SimpleXMLElement Object ( [PubmedArticle] => Array ( [0] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 33446526 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 09 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 09 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1095-9203 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 371 [Issue] => 6526 [PubDate] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 15 ) ) [Title] => Science (New York, N.Y.) [ISOAbbreviation] => Science ) [ArticleTitle] => Aberrant type 1 immunity drives susceptibility to mucosal fungal infections. [ELocationID] => Array ( [0] => eaay5731 [1] => 10.1126/science.aay5731 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. These responses promote aberrant interferon-γ (IFN-γ)- and signal transducer and activator of transcription 1 (STAT1)-dependent epithelial barrier defects as well as mucosal fungal infection susceptibility. Concordantly, genetic and pharmacologic inhibition of IFN-γ or Janus kinase (JAK)-STAT signaling ameliorates mucosal fungal disease. Thus, we identify aberrant T cell-dependent, type 1 mucosal inflammation as a critical tissue-specific pathogenic mechanism that promotes mucosal fungal infection susceptibility in mice and humans. [CopyrightInformation] => Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Break [ForeName] => Timothy J [Initials] => TJ [Identifier] => 0000-0001-5987-7817 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Oikonomou [ForeName] => Vasileios [Initials] => V [Identifier] => 0000-0002-7553-0159 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Dutzan [ForeName] => Nicolas [Initials] => N [Identifier] => 0000-0001-8343-0214 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Desai [ForeName] => Jigar V [Initials] => JV [Identifier] => 0000-0002-8823-0796 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swidergall [ForeName] => Marc [Initials] => M [Identifier] => 0000-0002-5261-6267 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ) ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Freiwald [ForeName] => Tilo [Initials] => T [Identifier] => 0000-0002-4759-717X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Chauss [ForeName] => Daniel [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Harrison [ForeName] => Oliver J [Initials] => OJ [Identifier] => 0000-0003-1515-9586 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Alejo [ForeName] => Julie [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Williams [ForeName] => Drake W [Initials] => DW [Identifier] => 0000-0002-7718-2098 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pittaluga [ForeName] => Stefania [Initials] => S [Identifier] => 0000-0001-7688-1439 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lee [ForeName] => Chyi-Chia R [Initials] => CR [Identifier] => 0000-0002-5306-7781 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bouladoux [ForeName] => Nicolas [Initials] => N [Identifier] => 0000-0003-1593-671X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [Identifier] => 0000-0002-8665-7016 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hoffman [ForeName] => Kevin W [Initials] => KW [Identifier] => 0000-0003-4284-4108 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Greenwell-Wild [ForeName] => Teresa [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bruno [ForeName] => Vincent M [Initials] => VM [Identifier] => 0000-0003-1683-2015 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rosen [ForeName] => Lindsey B [Initials] => LB [Identifier] => 0000-0001-5894-3878 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lwin [ForeName] => Wint [Initials] => W [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Diabetes Center, University of California, San Francisco, CA, USA. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Renteria [ForeName] => Andy [Initials] => A [Identifier] => 0000-0002-6978-1349 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pontejo [ForeName] => Sergio M [Initials] => SM [Identifier] => 0000-0002-7756-9831 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, Bethesda, MD, USA. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shannon [ForeName] => John P [Initials] => JP [Identifier] => 0000-0002-8722-2209 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Viral Immunity and Pathogenesis Unit, LCIM, NIAID, Bethesda, MD, USA. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Myles [ForeName] => Ian A [Initials] => IA [Identifier] => 0000-0001-9316-3703 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Epithelial Therapeutics Unit, LCIM, NIAID, Bethesda, MD, USA. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Olbrich [ForeName] => Peter [Initials] => P [Identifier] => 0000-0001-9853-7903 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ferré [ForeName] => Elise M N [Initials] => EMN [Identifier] => 0000-0002-3285-7768 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Schmitt [ForeName] => Monica [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. ) ) [26] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Martin [ForeName] => Daniel [Initials] => D [Identifier] => 0000-0002-8880-9087 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Genomics and Computational Biology Core, NIDCR, Bethesda, MD, USA. ) ) [27] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [CollectiveName] => Genomics and Computational Biology Core ) [28] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Barber [ForeName] => Daniel L [Initials] => DL [Identifier] => 0000-0003-0344-9447 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, NIAID, Bethesda, MD, USA. ) ) [29] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Solis [ForeName] => Norma V [Initials] => NV [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA. ) ) [30] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Notarangelo [ForeName] => Luigi D [Initials] => LD [Identifier] => 0000-0002-8335-0262 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immune Deficiency Genetics Section, LCIM, NIAID, Bethesda, MD, USA. ) ) [31] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Serreze [ForeName] => David V [Initials] => DV [Identifier] => 0000-0001-7614-5925 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Jackson Laboratory, Bar Harbor, ME, USA. ) ) [32] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Matsumoto [ForeName] => Mitsuru [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Tokushima, Japan. ) ) [33] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hickman [ForeName] => Heather D [Initials] => HD [Identifier] => 0000-0003-4168-4894 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Viral Immunity and Pathogenesis Unit, LCIM, NIAID, Bethesda, MD, USA. ) ) [34] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Murphy [ForeName] => Philip M [Initials] => PM [Identifier] => 0000-0002-1080-8201 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, Bethesda, MD, USA. ) ) [35] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Anderson [ForeName] => Mark S [Initials] => MS [Identifier] => 0000-0002-3093-4758 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Diabetes Center, University of California, San Francisco, CA, USA. ) ) [36] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lim [ForeName] => Jean K [Initials] => JK [Identifier] => 0000-0002-4572-6417 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ) ) [37] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [Identifier] => 0000-0003-3207-5464 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD, USA. ) ) [38] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Filler [ForeName] => Scott G [Initials] => SG [Identifier] => 0000-0001-7278-3700 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ) ) ) [39] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Afzali [ForeName] => Behdad [Initials] => B [Identifier] => 0000-0003-2968-1156 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA. ) ) [40] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Belkaid [ForeName] => Yasmine [Initials] => Y [Identifier] => 0000-0001-9962-3571 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Metaorganism Immunity Section, Laboratory of Immune System Biology, NIAID, Bethesda, MD, USA. ) ) [41] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Moutsopoulos [ForeName] => Niki M [Initials] => NM [Identifier] => 0000-0002-7365-6735 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA. ) ) [42] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [Identifier] => 0000-0003-4994-9500 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. lionakism@mail.nih.gov. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => R01 DE026600 [Acronym] => DE [Agency] => NIDCR NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => ZIC DC000086 [Acronym] => ImNIH [Agency] => Intramural NIH HHS [Country] => United States ) [2] => SimpleXMLElement Object ( [GrantID] => R01 AI124566 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) [3] => SimpleXMLElement Object ( [GrantID] => R00 DE026856 [Acronym] => DE [Agency] => NIDCR NIH HHS [Country] => United States ) [4] => SimpleXMLElement Object ( [GrantID] => R01 DK095735 [Acronym] => DK [Agency] => NIDDK NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Extramural [2] => Research Support, N.I.H., Intramural [3] => Research Support, Non-U.S. Gov't ) ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Science [NlmUniqueID] => 0404511 [ISSNLinking] => 0036-8075 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Interleukins ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Interleukin-17 ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => STAT1 Transcription Factor ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 82115-62-6 [NameOfSubstance] => Interferon-gamma ) [4] => SimpleXMLElement Object ( [RegistryNumber] => EC 2.7.10.2 [NameOfSubstance] => Janus Kinases ) [5] => SimpleXMLElement Object ( [RegistryNumber] => XEO71E2E45 [NameOfSubstance] => interleukin-22 ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Adolescent ) [1] => SimpleXMLElement Object ( [DescriptorName] => Adult ) [2] => SimpleXMLElement Object ( [DescriptorName] => Aged ) [3] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [4] => SimpleXMLElement Object ( [DescriptorName] => Candida albicans [QualifierName] => immunology ) [5] => SimpleXMLElement Object ( [DescriptorName] => Candidiasis, Chronic Mucocutaneous [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [6] => SimpleXMLElement Object ( [DescriptorName] => Disease Models, Animal ) [7] => SimpleXMLElement Object ( [DescriptorName] => Female ) [8] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [9] => SimpleXMLElement Object ( [DescriptorName] => Immunity, Mucosal [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [10] => SimpleXMLElement Object ( [DescriptorName] => Immunologic Surveillance [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [11] => SimpleXMLElement Object ( [DescriptorName] => Interferon-gamma [QualifierName] => genetics ) [12] => SimpleXMLElement Object ( [DescriptorName] => Interleukins [QualifierName] => genetics ) [13] => SimpleXMLElement Object ( [DescriptorName] => Janus Kinases [QualifierName] => genetics ) [14] => SimpleXMLElement Object ( [DescriptorName] => Male ) [15] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [16] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred BALB C ) [17] => SimpleXMLElement Object ( [DescriptorName] => Middle Aged ) [18] => SimpleXMLElement Object ( [DescriptorName] => Mouth Mucosa [QualifierName] => Array ( [0] => immunology [1] => pathology ) ) [19] => SimpleXMLElement Object ( [DescriptorName] => Polyendocrinopathies, Autoimmune [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [20] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Interleukin-17 [QualifierName] => genetics ) [21] => SimpleXMLElement Object ( [DescriptorName] => STAT1 Transcription Factor [QualifierName] => genetics ) [22] => SimpleXMLElement Object ( [DescriptorName] => T-Lymphocytes [QualifierName] => immunology ) [23] => SimpleXMLElement Object ( [DescriptorName] => Young Adult ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 07 [Day] => 02 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 07 [Day] => 05 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 11 [Day] => 13 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2021 [Month] => 1 [Day] => 15 [Hour] => 5 [Minute] => 46 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2021 [Month] => 1 [Day] => 16 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 2 [Day] => 10 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33446526 [1] => 371/6526/eaay5731 [2] => 10.1126/science.aay5731 ) ) ) ) [1] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Process [Owner] => NLM ) [PMID] => 32908007 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 20 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1946-6242 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 12 [Issue] => 560 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 09 [Day] => 09 ) ) [Title] => Science translational medicine [ISOAbbreviation] => Sci Transl Med ) [ArticleTitle] => Therapeutic responses to in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. [ELocationID] => Array ( [0] => eaaz8631 [1] => 10.1126/scitranslmed.aaz8631 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by , cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier. [CopyrightInformation] => Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Myles [ForeName] => Ian A [Initials] => IA [Identifier] => 0000-0001-9316-3703 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. mylesi@niaid.nih.gov. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Castillo [ForeName] => Carlo R [Initials] => CR [Identifier] => 0000-0002-1824-6696 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Barbian [ForeName] => Kent D [Initials] => KD [Identifier] => 0000-0001-9861-6150 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RTS Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kanakabandi [ForeName] => Kishore [Initials] => K [Identifier] => 0000-0003-3259-4459 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RTS Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Virtaneva [ForeName] => Kimmo [Initials] => K [Identifier] => 0000-0002-5503-1483 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RTS Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fitzmeyer [ForeName] => Emily [Initials] => E [Identifier] => 0000-0002-3962-190X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RTS Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Paneru [ForeName] => Monica [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RTS Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Otaizo-Carrasquero [ForeName] => Francisco [Initials] => F [Identifier] => 0000-0001-7518-173X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Genomic Technologies Section, NIAID, NIH, Bethesda, MD, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Myers [ForeName] => Timothy G [Initials] => TG [Identifier] => 0000-0002-7059-5906 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Genomic Technologies Section, NIAID, NIH, Bethesda, MD, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Markowitz [ForeName] => Tovah E [Initials] => TE [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => NIAID Collaborative Bioinformatics Resource (NCBR), NIAID, NIH, Bethesda, MD, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. ) ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Moore [ForeName] => Ian N [Initials] => IN [Identifier] => 0000-0002-0391-6466 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Disease Pathogenesis Section, Comparative Medicine Branch, NIAID, NIH, Rockville, MD, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Liu [ForeName] => Xue [Initials] => X [Identifier] => 0000-0002-0431-490X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pre-clinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ferrer [ForeName] => Marc [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pre-clinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD, USA. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sakamachi [ForeName] => Yosuke [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => National Institute of Environmental Health Sciences, Research Triangle, NC, USA. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Garantziotis [ForeName] => Stavros [Initials] => S [Identifier] => 0000-0003-4007-375X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => National Institute of Environmental Health Sciences, Research Triangle, NC, USA. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [Identifier] => 0000-0002-8665-7016 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD, USA. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD, USA. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Anderson [ForeName] => Erik D [Initials] => ED [Identifier] => 0000-0001-5329-4629 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Earland [ForeName] => Noah J [Initials] => NJ [Identifier] => 0000-0003-0170-407X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ganesan [ForeName] => Sundar [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biological Imaging Section, Research Technology Branch, NIAID, NIH, Bethesda, MD, USA. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sun [ForeName] => Ashleigh A [Initials] => AA [Identifier] => 0000-0003-3216-810X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bergerson [ForeName] => Jenna R E [Initials] => JRE [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Silverman [ForeName] => Robert A [Initials] => RA [Identifier] => 0000-0003-0674-4484 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Georgetown University Hospital, Washington, DC, USA. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Petersen [ForeName] => Maureen [Initials] => M [Identifier] => 0000-0003-1885-4664 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Walter Reed National Military Medical Center, Bethesda, MD, USA. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Martens [ForeName] => Craig A [Initials] => CA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RTS Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Datta [ForeName] => Sandip K [Initials] => SK [Identifier] => 0000-0003-0243-7815 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Intramural ) ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Sci Transl Med [NlmUniqueID] => 101505086 [ISSNLinking] => 1946-6234 ) [CitationSubset] => IM ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 10 [Day] => 16 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 01 [Day] => 03 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 03 [Day] => 12 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 9 [Day] => 10 [Hour] => 5 [Minute] => 29 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 9 [Day] => 11 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 9 [Day] => 11 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32908007 [1] => 12/560/eaaz8631 [2] => 10.1126/scitranslmed.aaz8631 ) ) ) ) [2] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Data-Review [Owner] => NLM ) [PMID] => 32432714 [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 08 [Day] => 20 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1537-6613 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 222 [Issue] => 6 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => Aug [Day] => 17 ) ) [Title] => The Journal of infectious diseases [ISOAbbreviation] => J Infect Dis ) [ArticleTitle] => Protective Activity of Programmed Cell Death Protein 1 Blockade and Synergy With Caspofungin in a Murine Invasive Pulmonary Aspergillosis Model. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 989-994 ) [ELocationID] => 10.1093/infdis/jiaa264 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Pharmacological immune checkpoint blockade has revolutionized oncological therapies, and its remarkable success has sparked interest in expanding checkpoint inhibitor therapy in infectious diseases. Herein, we evaluated the efficacy of programmed cell death protein 1 (PD-1) blockade in a murine invasive pulmonary aspergillosis model. We found that, compared with isotype-treated infected control mice, anti-PD-1-treated mice had improved survival, reduced fungal burden, increased lung concentrations of proinflammatory cytokines and neutrophil-attracting chemokines, and enhanced pulmonary leukocyte accumulation. Furthermore, combined treatment with anti-PD-1 and caspofungin resulted in a significant survival benefit compared with caspofungin or anti-PD-1 therapy alone, indicating a synergistic effect between PD-1 inhibitors and immunomodulatory antifungal agents. [CopyrightInformation] => Published by Oxford University Press for the Infectious Diseases Society of America 2020. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Wurster [ForeName] => Sebastian [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Robinson [ForeName] => Prema [Initials] => P [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Albert [ForeName] => Nathaniel D [Initials] => ND [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tarrand [ForeName] => Jeffrey J [Initials] => JJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Goff [ForeName] => Marisa [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lim [ForeName] => Jean K [Initials] => JK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kontoyiannis [ForeName] => Dimitrios P [Initials] => DP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Infect Dis [NlmUniqueID] => 0413675 [ISSNLinking] => 0022-1899 ) [CitationSubset] => Array ( [0] => AIM [1] => IM ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Antifungals [1] => Checkpoint inhibitors [2] => cytokines [3] => immunotherapy [4] => invasive aspergillosis ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 03 [Day] => 26 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 05 [Day] => 15 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pmc-release ) [Year] => 2021 [Month] => 08 [Day] => 17 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 5 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 5 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 5 [Day] => 21 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32432714 [1] => 5841121 [2] => 10.1093/infdis/jiaa264 [3] => PMC7430165 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Trends Mol Med. 2019 Dec;25(12):1080-1093 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31494023 ) ) [1] => SimpleXMLElement Object ( [Citation] => Front Microbiol. 2018 Jul 25;9:1612 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30090091 ) ) [2] => SimpleXMLElement Object ( [Citation] => Antimicrob Agents Chemother. 2001 Dec;45(12):3474-81 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11709327 ) ) [3] => SimpleXMLElement Object ( [Citation] => Clin Microbiol Rev. 2009 Oct;22(4):535-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19822887 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Immunol. 2017 Nov 15;199(10):3535-3546 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29038249 ) ) [5] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 2017 Dec 5;216(10):1281-1294 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28968869 ) ) [6] => SimpleXMLElement Object ( [Citation] => Crit Care. 2013 May 11;17(3):R85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23663657 ) ) [7] => SimpleXMLElement Object ( [Citation] => Shock. 2020 Apr;53(4):514-524 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31306346 ) ) [8] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Dec 17;11(12):e1005293 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26679537 ) ) [9] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 2008 Jul 15;198(2):186-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18500936 ) ) [10] => SimpleXMLElement Object ( [Citation] => Front Immunol. 2019 Mar 19;10:453 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30941125 ) ) [11] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4275-80 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20160101 ) ) [12] => SimpleXMLElement Object ( [Citation] => Antimicrob Agents Chemother. 2010 Mar;54(3):1298-304 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20038620 ) ) [13] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2658-63 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18268348 ) ) [14] => SimpleXMLElement Object ( [Citation] => Front Med (Lausanne). 2019 May 29;6:119 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31192215 ) ) ) ) ) ) [3] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Data-Review [Owner] => NLM ) [PMID] => 32311393 [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 11 [Day] => 17 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1097-6825 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 146 [Issue] => 5 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => Nov ) ) [Title] => The Journal of allergy and clinical immunology [ISOAbbreviation] => J Allergy Clin Immunol ) [ArticleTitle] => Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 1165-1179.e11 ) [ELocationID] => Array ( [0] => S0091-6749(20)30492-9 [1] => 10.1016/j.jaci.2020.04.005 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Array ( [0] => Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). [1] => The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. [2] => We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2 (Rag2) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. [3] => We show that memory/activated T cells from patients with OS and from the Rag2 mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad T1/T2/T17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2 mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2 mice results in increased frequency of Ccr4 splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by T1 effector T cells. [4] => These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS. ) [CopyrightInformation] => Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rigoni [ForeName] => Rosita [Initials] => R [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Milan Unit, Institute for Genetic and Biomedical Research (IRGB) National Research Council (CNR), Milan, Italy; Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fontana [ForeName] => Elena [Initials] => E [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Dobbs [ForeName] => Kerry [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Marrella [ForeName] => Veronica [Initials] => V [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Milan Unit, Institute for Genetic and Biomedical Research (IRGB) National Research Council (CNR), Milan, Italy; Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Taverniti [ForeName] => Valentina [Initials] => V [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Food, Environmental, and Nutritional Sciences, University of Milan Milan, Italy. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Maina [ForeName] => Virginia [Initials] => V [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Milan Unit, Institute for Genetic and Biomedical Research (IRGB) National Research Council (CNR), Milan, Italy; Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Facoetti [ForeName] => Amanda [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy; Humanitas University, Rozzano, Milan, Italy. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => D'Amico [ForeName] => Giovanna [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Centro Ricerca Tettamanti, Clinica Pediatrica, Università Milano-Bicocca, Monza, Italy. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Al-Herz [ForeName] => Waleed [Initials] => W [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; Allergy and Clinical Immunology Unit, Pediatric Department, Al-Sabah Hospital, Kuwait City, Kuwait. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Cruz-Munoz [ForeName] => Mario Ernesto [Initials] => ME [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Schuetz [ForeName] => Catharina [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Gennery [ForeName] => Andrew R [Initials] => AR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Great North Children's Hospital, Clinical Resource Building, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Garabedian [ForeName] => Elizabeth K [Initials] => EK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => National Human Genome Research Institute, NIH, Bethesda, Md. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Giliani [ForeName] => Silvia [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Cytogenetic and Medical Genetics Unit, "A. Nocivelli" Institute for Molecular Medicine, Spedali Civili Hospital, Brescia, Italy. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Draper [ForeName] => Deborah [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Dbaibo [ForeName] => Ghassan [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Geha [ForeName] => Raif S [Initials] => RS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Meyts [ForeName] => Isabelle [Initials] => I [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Universitair Ziekenhuis Leuven, University Hospitals Leuven, Leuven, Belgium; Laboratory for Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tousseyn [ForeName] => Thomas [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Lab for Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Leuven, Belgium. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Neven [ForeName] => Benedicte [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris, France; Pediatric Immuno-Hematology Unit, Necker Children Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Moshous [ForeName] => Despina [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris, France; Pediatric Immuno-Hematology Unit, Necker Children Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fischer [ForeName] => Alain [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris, France; Pediatric Immuno-Hematology Unit, Necker Children Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Schulz [ForeName] => Ansgar [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Finocchi [ForeName] => Andrea [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Children's Hospital Bambino Gesù, Rome, Italy. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kuhns [ForeName] => Douglas B [Initials] => DB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Md. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fink [ForeName] => Danielle L [Initials] => DL [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Md. ) ) [26] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md. ) ) [27] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Md. ) ) [28] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Guglielmetti [ForeName] => Simone [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Food, Environmental, and Nutritional Sciences, University of Milan Milan, Italy. ) ) [29] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Alejo [ForeName] => Julie [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md. ) ) [30] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Myles [ForeName] => Ian A [Initials] => IA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md. ) ) [31] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pittaluga [ForeName] => Stefania [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md. ) ) [32] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Notarangelo [ForeName] => Luigi D [Initials] => LD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md. Electronic address: luigi.notarangelo2@nih.gov. ) ) [33] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Villa [ForeName] => Anna [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Milan Unit, Institute for Genetic and Biomedical Research (IRGB) National Research Council (CNR), Milan, Italy; Telethon Institute for Gene Therapy, Division of Regenerative Medicine, Stem Cells, and Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: villa.anna@hsr.it. ) ) [34] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Cassani [ForeName] => Barbara [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Milan Unit, Institute for Genetic and Biomedical Research (IRGB) National Research Council (CNR), Milan, Italy; Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy. Electronic address: barbara.cassani@humanitasresearch.it. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 04 [Day] => 18 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Allergy Clin Immunol [NlmUniqueID] => 1275002 [ISSNLinking] => 0091-6749 ) [CitationSubset] => Array ( [0] => AIM [1] => IM ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => LPS [1] => RAG [2] => T cells [3] => chemokines [4] => cytokines [5] => dysbiosis [6] => erythroderma [7] => gut-skin axis [8] => immune-mediated disease [9] => skin inflammation ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 09 [Day] => 18 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 03 [Day] => 11 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 04 [Day] => 06 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 4 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 4 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 4 [Day] => 21 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32311393 [1] => S0091-6749(20)30492-9 [2] => 10.1016/j.jaci.2020.04.005 [3] => PMC7649331 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => JCI Insight. 2016 Jul 7;1(10): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27478874 ) ) [1] => SimpleXMLElement Object ( [Citation] => PLoS One. 2014 Mar 11;9(3):e91054 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24618819 ) ) [2] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2016 Apr;16(4):234-46 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26996199 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Leukoc Biol. 2013 Dec;94(6):1221-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24052573 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Immunol. 2006 Sep 1;177(5):3369-79 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16920978 ) ) [5] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2016 Mar 7;213(3):355-75 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26926994 ) ) [6] => SimpleXMLElement Object ( [Citation] => Clin Rev Allergy Immunol. 2014 Apr;46(2):112-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23760761 ) ) [7] => SimpleXMLElement Object ( [Citation] => Front Physiol. 2012 Feb 06;3:13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22347192 ) ) [8] => SimpleXMLElement Object ( [Citation] => Annu Rev Immunol. 2017 Apr 26;35:31-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27860528 ) ) [9] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2014 May;14(5):289-301 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24722477 ) ) [10] => SimpleXMLElement Object ( [Citation] => Science. 2012 Aug 31;337(6098):1115-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22837383 ) ) [11] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2017 Apr;137(4):855-864 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27887954 ) ) [12] => SimpleXMLElement Object ( [Citation] => Drugs. 2012 Jun 18;72(9):1293-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22686619 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Leukoc Biol. 2001 Oct;70(4):617-23 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11590199 ) ) [14] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2002 Aug;119(2):424-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12190866 ) ) [15] => SimpleXMLElement Object ( [Citation] => J Immunol. 2013 Feb 1;190(3):970-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23255361 ) ) [16] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2008 Nov;128(11):2569-2571 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18927538 ) ) [17] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 1994 Jul;94(1):202-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8040262 ) ) [18] => SimpleXMLElement Object ( [Citation] => Curr Top Microbiol Immunol. 2006;308:83-116 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16922087 ) ) [19] => SimpleXMLElement Object ( [Citation] => J Cell Biol. 2006 Nov 20;175(4):661-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17116754 ) ) [20] => SimpleXMLElement Object ( [Citation] => Front Immunol. 2019 Jun 25;10:1440 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31293591 ) ) [21] => SimpleXMLElement Object ( [Citation] => Pediatr Dev Pathol. 2001 May-Jun;4(3):237-45 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11370261 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Immunol. 2001 Jan 1;166(1):103-11 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11123282 ) ) [23] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2008 Apr;128(4):917-25 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17943185 ) ) [24] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2011 Jun;121(6):2210-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21537081 ) ) [25] => SimpleXMLElement Object ( [Citation] => Nucleic Acids Res. 2013 Jan;41(Database issue):D590-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23193283 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2009 Nov;129(11):2552-66 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19474804 ) ) [27] => SimpleXMLElement Object ( [Citation] => Nature. 1999 Aug 19;400(6746):776-80 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10466728 ) ) [28] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2002 Nov;32(11):3171-80 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12555662 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2008 Jan;121(1):129-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18028995 ) ) [30] => SimpleXMLElement Object ( [Citation] => Nat Med. 2002 Feb;8(2):157-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11821900 ) ) [31] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2009 Oct;9(10):679-91 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19763149 ) ) [32] => SimpleXMLElement Object ( [Citation] => PLoS One. 2008 Jul 23;3(7):e2719 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18648509 ) ) [33] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2007 May;117(5):1260-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17476358 ) ) [34] => SimpleXMLElement Object ( [Citation] => Pediatr Crit Care Med. 2005 May;6(3 Suppl):S99-S107 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15857568 ) ) [35] => SimpleXMLElement Object ( [Citation] => Genome Biol. 2011 Jun 24;12(6):R60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21702898 ) ) [36] => SimpleXMLElement Object ( [Citation] => Genome Res. 2013 Dec;23(12):2103-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24170601 ) ) [37] => SimpleXMLElement Object ( [Citation] => J Am Acad Dermatol. 2013 May;68(5):875-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23602178 ) ) [38] => SimpleXMLElement Object ( [Citation] => Nat Rev Gastroenterol Hepatol. 2015 Oct;12(10):561-71 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26260366 ) ) [39] => SimpleXMLElement Object ( [Citation] => Inflamm Bowel Dis. 2010 Nov;16(11):1969-77 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20848507 ) ) [40] => SimpleXMLElement Object ( [Citation] => Genome Res. 2012 May;22(5):850-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22310478 ) ) [41] => SimpleXMLElement Object ( [Citation] => Dermatology. 2006;213(4):284-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17135733 ) ) [42] => SimpleXMLElement Object ( [Citation] => J Immunol. 2008 Jan 1;180(1):122-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18097011 ) ) [43] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2006 Feb 9;354(6):610-21 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16467548 ) ) [44] => SimpleXMLElement Object ( [Citation] => Nature. 1997 Oct 30;389(6654):978-81 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9353122 ) ) [45] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2001 Nov 19;194(10):1541-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11714760 ) ) [46] => SimpleXMLElement Object ( [Citation] => Clin Mol Allergy. 2008 Sep 22;6:11 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18808715 ) ) [47] => SimpleXMLElement Object ( [Citation] => Nat Methods. 2010 May;7(5):335-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20383131 ) ) [48] => SimpleXMLElement Object ( [Citation] => PLoS One. 2013 Jul 15;8(7):e68739 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23869230 ) ) [49] => SimpleXMLElement Object ( [Citation] => J Exp Med. 1991 Dec 1;174(6):1461-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1720810 ) ) [50] => SimpleXMLElement Object ( [Citation] => Semin Immunopathol. 2007 Apr;29(1):3-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17621950 ) ) [51] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2015 Sep 29;6:8424 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26416167 ) ) [52] => SimpleXMLElement Object ( [Citation] => Nature. 2011 Aug 14;477(7363):216-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21841802 ) ) [53] => SimpleXMLElement Object ( [Citation] => Gut Microbes. 2016 Nov;7(6):503-511 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27575988 ) ) [54] => SimpleXMLElement Object ( [Citation] => Clin Gastroenterol Hepatol. 2008 Jul;6(7):759-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18456568 ) ) [55] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2001 Feb;116(2):330-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11180011 ) ) ) ) ) ) [4] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32132174 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 12 [Day] => 17 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 05 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1083-351X [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 295 [Issue] => 16 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 04 [Day] => 17 ) ) [Title] => The Journal of biological chemistry [ISOAbbreviation] => J Biol Chem ) [ArticleTitle] => Development of a novel β-1,6-glucan-specific detection system using functionally-modified recombinant endo-β-1,6-glucanase. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 5362-5376 ) [ELocationID] => 10.1074/jbc.RA119.011851 [Abstract] => SimpleXMLElement Object ( [AbstractText] => β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a of 16.4 nm We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen , without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different species (including ) in culture supernatant We also used this assay to measure β-1,6-glucan in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections. [CopyrightInformation] => © 2020 Yamanaka et al. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yamanaka [ForeName] => Daisuke [Initials] => D [Identifier] => 0000-0002-0046-7052 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan ymnkd@toyaku.ac.jp. ) [1] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Takatsu [ForeName] => Kazushiro [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kimura [ForeName] => Masahiro [Initials] => M [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo 192-0015, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Research Fellow of Japan Society for the Promotion of Science (DC2), Koujimachi, Chiyoda-ku, Tokyo 102-0083, Japan. ) ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [Identifier] => 0000-0002-8665-7016 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ohnishi [ForeName] => Hiroaki [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Laboratory Medicine, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Umeyama [ForeName] => Takashi [Initials] => T [Identifier] => 0000-0002-6635-4288 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Oyama [ForeName] => Fumitaka [Initials] => F [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo 192-0015, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ohno [ForeName] => Naohito [Initials] => N [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => SimpleXMLElement Object ( [GrantID] => ZIA AI001175 [Acronym] => ImNIH [Agency] => Intramural NIH HHS [Country] => United States ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Intramural [2] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 03 [Day] => 04 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Biol Chem [NlmUniqueID] => 2985121R [ISSNLinking] => 0021-9258 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Fungal Polysaccharides ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Polysaccharides ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Recombinant Proteins ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => beta-Glucans ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 37331-28-5 [NameOfSubstance] => pustulan ) [5] => SimpleXMLElement Object ( [RegistryNumber] => 37361-00-5 [NameOfSubstance] => beta-1,6-glucan ) [6] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.2.1.- [NameOfSubstance] => Glycoside Hydrolases ) [7] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.2.1.75 [NameOfSubstance] => endo-1,6-beta-glucanase ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Biosensing Techniques [QualifierName] => methods ) [2] => SimpleXMLElement Object ( [DescriptorName] => Candida [QualifierName] => metabolism ) [3] => SimpleXMLElement Object ( [DescriptorName] => Enzyme Assays [QualifierName] => methods ) [4] => SimpleXMLElement Object ( [DescriptorName] => Female ) [5] => SimpleXMLElement Object ( [DescriptorName] => Fungal Polysaccharides [QualifierName] => Array ( [0] => chemistry [1] => metabolism ) ) [6] => SimpleXMLElement Object ( [DescriptorName] => Glycoside Hydrolases [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [7] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [8] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred C57BL ) [9] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred ICR ) [10] => SimpleXMLElement Object ( [DescriptorName] => Polysaccharides [QualifierName] => Array ( [0] => analysis [1] => metabolism ) ) [11] => SimpleXMLElement Object ( [DescriptorName] => Recombinant Proteins [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [12] => SimpleXMLElement Object ( [DescriptorName] => beta-Glucans [QualifierName] => Array ( [0] => analysis [1] => metabolism ) ) ) ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Candida albicans [1] => animal model [2] => deep mycosis [3] => endo-β-1,6-glucanase [4] => fungi [5] => glycobiology [6] => glycoside hydrolase [7] => infectious disease [8] => β-1,3-D-glucan [9] => β-1,6-glucan ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 11 [Day] => 11 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 02 [Day] => 28 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 3 [Day] => 7 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 12 [Day] => 18 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 3 [Day] => 6 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32132174 [1] => S0021-9258(17)48555-3 [2] => 10.1074/jbc.RA119.011851 [3] => PMC7170528 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2013 Dec;123(12):5035-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24177428 ) ) [1] => SimpleXMLElement Object ( [Citation] => Carbohydr Res. 1996 Dec 13;295:103-16 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9002187 ) ) [2] => SimpleXMLElement Object ( [Citation] => Glycoconj J. 2008 Dec;25(9):851-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18587644 ) ) [3] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2009 Apr 30;360(18):1870-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19403905 ) ) [4] => SimpleXMLElement Object ( [Citation] => Arch Biochem Biophys. 1968 Mar 20;124(1):292-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 4298494 ) ) [5] => SimpleXMLElement Object ( [Citation] => Carbohydr Res. 1996 Feb 23;281(2):187-201 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8721145 ) ) [6] => SimpleXMLElement Object ( [Citation] => FEMS Immunol Med Microbiol. 1999 Jul 15;24(4):411-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10435760 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Immunol Methods. 2011 Feb 28;365(1-2):158-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21184758 ) ) [8] => SimpleXMLElement Object ( [Citation] => Biosci Biotechnol Biochem. 2002 Jun;66(6):1378-81 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12162562 ) ) [9] => SimpleXMLElement Object ( [Citation] => Nihon Ishinkin Gakkai Zasshi. 2010;51(2):99-107 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20467198 ) ) [10] => SimpleXMLElement Object ( [Citation] => Carbohydr Res. 1971 Nov;20(1):185-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 5151193 ) ) [11] => SimpleXMLElement Object ( [Citation] => J Lab Clin Med. 1996 Jul;128(1):103-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8759942 ) ) [12] => SimpleXMLElement Object ( [Citation] => Clin Microbiol Rev. 2014 Jul;27(3):490-526 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24982319 ) ) [13] => SimpleXMLElement Object ( [Citation] => Carbohydr Res. 1999 Mar 31;316(1-4):161-72 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10420595 ) ) [14] => SimpleXMLElement Object ( [Citation] => PLoS Biol. 2018 Oct 12;16(10):e2006607 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30312293 ) ) [15] => SimpleXMLElement Object ( [Citation] => Int Immunopharmacol. 2012 Nov;14(3):311-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22878139 ) ) [16] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2001 Jun;69(6):3933-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11349061 ) ) [17] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2017 Jun 23;292(25):10639-10650 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28461332 ) ) [18] => SimpleXMLElement Object ( [Citation] => FEMS Immunol Med Microbiol. 2000 Sep;29(1):69-76 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10967263 ) ) [19] => SimpleXMLElement Object ( [Citation] => J Immunol Methods. 2008 Aug 20;337(1):55-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18589436 ) ) [20] => SimpleXMLElement Object ( [Citation] => J Agric Food Chem. 2017 Dec 20;65(50):10837-10843 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29136374 ) ) [21] => SimpleXMLElement Object ( [Citation] => PLoS One. 2011;6(11):e27614 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22096604 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Bacteriol. 1983 Apr;154(1):161-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 6300031 ) ) [23] => SimpleXMLElement Object ( [Citation] => Carbohydr Polym. 2015 Nov 5;132:304-10 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26256353 ) ) [24] => SimpleXMLElement Object ( [Citation] => Nat Rev Dis Primers. 2018 May 11;4:18026 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29749387 ) ) [25] => SimpleXMLElement Object ( [Citation] => Carbohydr Polym. 2017 May 15;164:145-153 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28325311 ) ) [26] => SimpleXMLElement Object ( [Citation] => Microbiol Immunol. 2009 Jan;53(1):41-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19161556 ) ) [27] => SimpleXMLElement Object ( [Citation] => J Immunol. 2014 Feb 1;192(3):1302-12 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24391208 ) ) [28] => SimpleXMLElement Object ( [Citation] => Arch Pathol Lab Med. 2016 Feb;140(2):181-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26910223 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Immunol Methods. 2006 Jul 31;314(1-2):164-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16844139 ) ) [30] => SimpleXMLElement Object ( [Citation] => Appl Microbiol Biotechnol. 2017 Jan;101(1):197-204 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27521023 ) ) [31] => SimpleXMLElement Object ( [Citation] => Immunity. 2003 Sep;19(3):311-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14499107 ) ) [32] => SimpleXMLElement Object ( [Citation] => Biosci Biotechnol Biochem. 2005 Mar;69(3):553-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15784984 ) ) [33] => SimpleXMLElement Object ( [Citation] => Eur J Biochem. 2001 May;268(9):2616-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11322881 ) ) [34] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [35] => SimpleXMLElement Object ( [Citation] => Int J Biol Macromol. 2018 Feb;107(Pt B):2269-2278 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29051097 ) ) [36] => SimpleXMLElement Object ( [Citation] => J Pharm Sci. 2012 Jan;101(1):256-67 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21953550 ) ) [37] => SimpleXMLElement Object ( [Citation] => Int J Mol Sci. 2019 Jul 16;20(14): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31315292 ) ) [38] => SimpleXMLElement Object ( [Citation] => FEMS Immunol Med Microbiol. 2005 Apr 1;44(1):99-109 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15780582 ) ) [39] => SimpleXMLElement Object ( [Citation] => Biol Pharm Bull. 2000 Jul;23(7):866-72 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10919368 ) ) [40] => SimpleXMLElement Object ( [Citation] => Carbohydr Polym. 2008 Sep 5;73(4):515-31 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26048217 ) ) [41] => SimpleXMLElement Object ( [Citation] => ACS Chem Biol. 2012 Nov 16;7(11):1848-57 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22894855 ) ) [42] => SimpleXMLElement Object ( [Citation] => Biochem Biophys Res Commun. 1986 Dec 30;141(3):1177-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 3028389 ) ) [43] => SimpleXMLElement Object ( [Citation] => FEMS Immunol Med Microbiol. 2004 Oct 1;42(2):155-66 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15364099 ) ) [44] => SimpleXMLElement Object ( [Citation] => Carbohydr Res. 2007 Dec 10;342(17):2611-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17868661 ) ) [45] => SimpleXMLElement Object ( [Citation] => Nature. 2001 Sep 6;413(6851):36-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11544516 ) ) [46] => SimpleXMLElement Object ( [Citation] => Biochem Biophys Res Commun. 1999 Jun 24;260(1):89-93 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10381348 ) ) [47] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2006 Apr;74(4):2373-81 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16552067 ) ) [48] => SimpleXMLElement Object ( [Citation] => Carbohydr Res. 1976 Jun;48(2):209-16 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 947537 ) ) [49] => SimpleXMLElement Object ( [Citation] => Anal Biochem. 1999 Oct 15;274(2):229-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10527520 ) ) [50] => SimpleXMLElement Object ( [Citation] => PLoS One. 2019 Apr 25;14(4):e0215535 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31022215 ) ) [51] => SimpleXMLElement Object ( [Citation] => Lancet. 1995 Jan 7;345(8941):17-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7799700 ) ) [52] => SimpleXMLElement Object ( [Citation] => Jpn J Surg. 1984 Jul;14(4):286-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 6238190 ) ) [53] => SimpleXMLElement Object ( [Citation] => Planta. 1991 Aug;185(1):1-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24186272 ) ) [54] => SimpleXMLElement Object ( [Citation] => Biochem J. 1990 Sep 15;270(3):705-13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2241903 ) ) ) ) ) ) [5] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 31167928 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 06 [Day] => 29 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 09 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1946-6242 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 11 [Issue] => 495 [PubDate] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 06 [Day] => 05 ) ) [Title] => Science translational medicine [ISOAbbreviation] => Sci Transl Med ) [ArticleTitle] => Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance. [ELocationID] => Array ( [0] => eaav5597 [1] => 10.1126/scitranslmed.aav5597 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by mutations, presents with several autoimmune diseases. Among these, endocrine organ failure is widely recognized, but the prevalence, immunopathogenesis, and treatment of non-endocrine manifestations such as pneumonitis remain poorly characterized. We enrolled 50 patients with APECED in a prospective observational study and comprehensively examined their clinical and radiographic findings, performed pulmonary function tests, and analyzed immunological characteristics in blood, bronchoalveolar lavage fluid, and endobronchial and lung biopsies. Pneumonitis was found in >40% of our patients, presented early in life, was misdiagnosed despite chronic respiratory symptoms and accompanying radiographic and pulmonary function abnormalities, and caused hypoxemic respiratory failure and death. Autoantibodies against BPIFB1 and KCNRG and the homozygous c.967_979del13 mutation are associated with pneumonitis development. APECED pneumonitis features compartmentalized immunopathology, with accumulation of activated neutrophils in the airways and lymphocytic infiltration in intraepithelial, submucosal, peribronchiolar, and interstitial areas. Beyond APECED, we extend these observations to lung disease seen in other conditions with secondary AIRE deficiency (thymoma and RAG deficiency). Aire-deficient mice had similar compartmentalized cellular immune responses in the airways and lung tissue, which was ameliorated by deficiency of T and B lymphocytes. Accordingly, T and B lymphocyte-directed immunomodulation controlled symptoms and radiographic abnormalities and improved pulmonary function in patients with APECED pneumonitis. Collectively, our findings unveil lung autoimmunity as a common, early, and unrecognized manifestation of APECED and provide insights into the immunopathogenesis and treatment of pulmonary autoimmunity associated with impaired central immune tolerance. [CopyrightInformation] => Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ferré [ForeName] => Elise M N [Initials] => EMN [Identifier] => 0000-0002-3285-7768 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Break [ForeName] => Timothy J [Initials] => TJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Burbelo [ForeName] => Peter D [Initials] => PD [Identifier] => 0000-0003-1717-048X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Dental Clinical Research Core, National Institute of Dental and Craniofacial Research (NIDCR), NIH, Bethesda, MD 20892, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Allgäuer [ForeName] => Michael [Initials] => M [Identifier] => 0000-0003-4518-7887 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. ) ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kleiner [ForeName] => David E [Initials] => DE [Identifier] => 0000-0003-3442-4453 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Jin [ForeName] => Dakai [Initials] => D [Identifier] => 0000-0002-4806-2943 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Radiology and Imaging Sciences, NIH Clinical Center (CC), NIH, Bethesda, MD 20892, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Xu [ForeName] => Ziyue [Initials] => Z [Identifier] => 0000-0002-5728-6869 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Radiology and Imaging Sciences, NIH Clinical Center (CC), NIH, Bethesda, MD 20892, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Folio [ForeName] => Les R [Initials] => LR [Identifier] => 0000-0003-2655-7483 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Radiology and Imaging Sciences, NIH Clinical Center (CC), NIH, Bethesda, MD 20892, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mollura [ForeName] => Daniel J [Initials] => DJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Radiology and Imaging Sciences, NIH Clinical Center (CC), NIH, Bethesda, MD 20892, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [Identifier] => 0000-0002-8665-7016 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Gu [ForeName] => Wenjuan [Initials] => W [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biostatistics Research Branch, Division of Clinical Research (DCR), NIAID, NIH, Bethesda, MD 20892, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hunsberger [ForeName] => Sally [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biostatistics Research Branch, Division of Clinical Research (DCR), NIAID, NIH, Bethesda, MD 20892, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lee [ForeName] => Chyi-Chia R [Initials] => CR [Identifier] => 0000-0002-5306-7781 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bondici [ForeName] => Anamaria [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hoffman [ForeName] => Kevin W [Initials] => KW [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lim [ForeName] => Jean K [Initials] => JK [Identifier] => 0000-0002-4572-6417 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Dobbs [ForeName] => Kerry [Initials] => K [Identifier] => 0000-0002-3432-3137 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immune Deficiency Genetics Section, LCIM, NIAID, NIH, Bethesda, MD 20892, USA. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Niemela [ForeName] => Julie E [Initials] => JE [Identifier] => 0000-0003-4197-3792 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine (DLM), NIH CC, NIH, Bethesda, MD 20892, USA. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fleisher [ForeName] => Thomas A [Initials] => TA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine (DLM), NIH CC, NIH, Bethesda, MD 20892, USA. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hsu [ForeName] => Amy P [Initials] => AP [Identifier] => 0000-0001-6841-2122 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD 20892, USA. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Snow [ForeName] => Laquita N [Initials] => LN [Identifier] => 0000-0001-8395-0746 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Darnell [ForeName] => Dirk N [Initials] => DN [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ojaimi [ForeName] => Samar [Initials] => S [Identifier] => 0000-0003-2129-1866 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Monash Health, Melbourne, VIC 3800, Australia. ) [1] => SimpleXMLElement Object ( [Affiliation] => Centre for Inflammatory Diseases, Monash University, Melbourne, VIC 3800, Australia. ) ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Cooper [ForeName] => Megan A [Initials] => MA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bozzola [ForeName] => Martin [Initials] => M [Identifier] => 0000-0003-3718-7086 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, British Hospital, Perdriel 74, CABA-Buenos Aires, Argentina. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kleiner [ForeName] => Gary I [Initials] => GI [Identifier] => 0000-0003-2066-9476 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => University of Miami Department of Pediatrics, Miami, FL 33136, USA. ) ) [26] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Martinez [ForeName] => Juan C [Initials] => JC [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Cystic Fibrosis, Pulmonary, and Sleep Division, Joe DiMaggio Children's Hospital, Hollywood, FL 33021, USA. ) ) [27] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Deterding [ForeName] => Robin R [Initials] => RR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA. ) ) [28] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kuhns [ForeName] => Douglas B [Initials] => DB [Identifier] => 0000-0002-9971-0760 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Neutrophil Monitoring Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21701, USA. ) ) [29] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Heller [ForeName] => Theo [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. ) ) [30] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Winer [ForeName] => Karen K [Initials] => KK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Pediatric Growth and Nutrition Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD 20892, USA. ) ) [31] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rajan [ForeName] => Arun [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. ) ) [32] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [Identifier] => 0000-0003-3207-5464 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD 20892, USA. ) ) [33] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Notarangelo [ForeName] => Luigi D [Initials] => LD [Identifier] => 0000-0002-8335-0262 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immune Deficiency Genetics Section, LCIM, NIAID, NIH, Bethesda, MD 20892, USA. ) ) [34] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fennelly [ForeName] => Kevin P [Initials] => KP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Chronic Airway Infection, Pulmonary Branch, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD 20892, USA. ) ) [35] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Olivier [ForeName] => Kenneth N [Initials] => KN [Identifier] => 0000-0001-8200-255X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Chronic Airway Infection, Pulmonary Branch, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD 20892, USA. ) ) [36] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [Identifier] => 0000-0003-4994-9500 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. lionakism@mail.nih.gov. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001C [Acronym] => RC [Agency] => CCR NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001E [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) [2] => SimpleXMLElement Object ( [GrantID] => U54 HL096458 [Acronym] => HL [Agency] => NHLBI NIH HHS [Country] => United States ) [3] => SimpleXMLElement Object ( [GrantID] => Z99 AI999999 [Acronym] => ImNIH [Agency] => Intramural NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Extramural [2] => Research Support, N.I.H., Intramural ) ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Sci Transl Med [NlmUniqueID] => 101505086 [ISSNLinking] => 1946-6234 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Autoantibodies ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Adolescent ) [1] => SimpleXMLElement Object ( [DescriptorName] => Adult ) [2] => SimpleXMLElement Object ( [DescriptorName] => Autoantibodies [QualifierName] => immunology ) [3] => SimpleXMLElement Object ( [DescriptorName] => Autoimmune Diseases [QualifierName] => Array ( [0] => immunology [1] => metabolism [2] => pathology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Autoimmunity [QualifierName] => physiology ) [5] => SimpleXMLElement Object ( [DescriptorName] => B-Lymphocytes [QualifierName] => Array ( [0] => immunology [1] => metabolism ) ) [6] => SimpleXMLElement Object ( [DescriptorName] => Child ) [7] => SimpleXMLElement Object ( [DescriptorName] => Child, Preschool ) [8] => SimpleXMLElement Object ( [DescriptorName] => Female ) [9] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [10] => SimpleXMLElement Object ( [DescriptorName] => Infant ) [11] => SimpleXMLElement Object ( [DescriptorName] => Infant, Newborn ) [12] => SimpleXMLElement Object ( [DescriptorName] => Lymphocytes [QualifierName] => Array ( [0] => immunology [1] => metabolism ) ) [13] => SimpleXMLElement Object ( [DescriptorName] => Male ) [14] => SimpleXMLElement Object ( [DescriptorName] => Middle Aged ) [15] => SimpleXMLElement Object ( [DescriptorName] => Pneumonia [QualifierName] => Array ( [0] => immunology [1] => metabolism [2] => pathology ) ) [16] => SimpleXMLElement Object ( [DescriptorName] => Prospective Studies ) [17] => SimpleXMLElement Object ( [DescriptorName] => T-Lymphocytes [QualifierName] => Array ( [0] => immunology [1] => metabolism ) ) [18] => SimpleXMLElement Object ( [DescriptorName] => Young Adult ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2018 [Month] => 09 [Day] => 28 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2019 [Month] => 04 [Day] => 05 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2019 [Month] => 6 [Day] => 7 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2019 [Month] => 6 [Day] => 7 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 7 [Day] => 1 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 31167928 [1] => 11/495/eaav5597 [2] => 10.1126/scitranslmed.aav5597 [3] => PMC6647037 [4] => NIHMS1041540 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Ann Rheum Dis. 1999 Jan;58(1):61-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10343542 ) ) [1] => SimpleXMLElement Object ( [Citation] => Curr Opin Pulm Med. 2000 Sep;6(5):424-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10958234 ) ) [2] => SimpleXMLElement Object ( [Citation] => Clin Endocrinol (Oxf). 2001 Feb;54(2):211-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11207636 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2001 Oct;86(10):4747-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11600535 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Med Genet. 1992 Nov;29(11):824-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1453436 ) ) [5] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2005 Aug;90(8):4930-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15886230 ) ) [6] => SimpleXMLElement Object ( [Citation] => Immunity. 2005 Aug;23(2):227-39 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16111640 ) ) [7] => SimpleXMLElement Object ( [Citation] => Neuroimage. 2006 Jul 1;31(3):1116-28 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16545965 ) ) [8] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2006 Aug;91(8):2843-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16684821 ) ) [9] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2006 Jul 1;43(1):16-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16758413 ) ) [10] => SimpleXMLElement Object ( [Citation] => Clin Genet. 2006 Oct;70(4):348-54 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16965330 ) ) [11] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2007 Feb;92(2):595-603 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17118990 ) ) [12] => SimpleXMLElement Object ( [Citation] => J Pediatr Endocrinol Metab. 2006 Nov;19(11):1343-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17220063 ) ) [13] => SimpleXMLElement Object ( [Citation] => Am J Med. 1991 Dec;91(6):625-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1750432 ) ) [14] => SimpleXMLElement Object ( [Citation] => Eur J Endocrinol. 2008 May;158(5):705-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18426830 ) ) [15] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13009-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18755889 ) ) [16] => SimpleXMLElement Object ( [Citation] => J Immunol. 2008 Sep 15;181(6):4072-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18768863 ) ) [17] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4396-401 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19251657 ) ) [18] => SimpleXMLElement Object ( [Citation] => Annu Rev Immunol. 2009;27:287-312 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19302042 ) ) [19] => SimpleXMLElement Object ( [Citation] => Horm Res Paediatr. 2010;73(6):449-57 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20407228 ) ) [20] => SimpleXMLElement Object ( [Citation] => Blood. 2010 Aug 26;116(8):1263-71 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20489056 ) ) [21] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14709-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20668237 ) ) [22] => SimpleXMLElement Object ( [Citation] => Eur Respir J. 2011 Jun;37(6):1411-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20884744 ) ) [23] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [24] => SimpleXMLElement Object ( [Citation] => Comput Med Imaging Graph. 2012 Apr;36(3):227-38 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21803548 ) ) [25] => SimpleXMLElement Object ( [Citation] => Pediatr Pulmonol. 2012 Jan;47(1):84-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21901851 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2012 Apr;97(4):1114-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22344197 ) ) [27] => SimpleXMLElement Object ( [Citation] => J Clin Immunol. 2013 Jan;33(1):30-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22930256 ) ) [28] => SimpleXMLElement Object ( [Citation] => J Inflamm Res. 2013;6:1-11 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23426081 ) ) [29] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 1990 Jun 28;322(26):1829-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2348835 ) ) [30] => SimpleXMLElement Object ( [Citation] => Sci Transl Med. 2013 Oct 9;5(206):206ra139 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24107778 ) ) [31] => SimpleXMLElement Object ( [Citation] => J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1257-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24945421 ) ) [32] => SimpleXMLElement Object ( [Citation] => Horm Res Paediatr. 2014;82(2):127-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25059117 ) ) [33] => SimpleXMLElement Object ( [Citation] => J Immunol. 2014 Oct 15;193(8):3880-90 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25230752 ) ) [34] => SimpleXMLElement Object ( [Citation] => Science. 2015 May 1;348(6234):589-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25791085 ) ) [35] => SimpleXMLElement Object ( [Citation] => Respirology. 2015 Oct;20(7):1073-81 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26122009 ) ) [36] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2015 Nov 2;125(11):4135-48 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26457731 ) ) [37] => SimpleXMLElement Object ( [Citation] => Eur Respir J. 1989 Jun;2(6):561-85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2663535 ) ) [38] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Dec 17;11(12):e1005293 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26679537 ) ) [39] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2016 Aug;101(8):2975-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27253668 ) ) [40] => SimpleXMLElement Object ( [Citation] => Br J Dermatol. 2017 Feb;176(2):395-402 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27452897 ) ) [41] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2016 Oct 3;126(10):3758-3771 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27571405 ) ) [42] => SimpleXMLElement Object ( [Citation] => JCI Insight. 2016 Aug 18;1(13):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27588307 ) ) [43] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2017 Sep 1;102(9):3546-3556 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28911151 ) ) [44] => SimpleXMLElement Object ( [Citation] => Curr Opin Immunol. 2017 Dec;49:71-78 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29065385 ) ) [45] => SimpleXMLElement Object ( [Citation] => Sci Rep. 2017 Dec 4;7(1):16878 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29203879 ) ) [46] => SimpleXMLElement Object ( [Citation] => Comput Methods Biomech Biomed Eng Imaging Vis. 2018;6(1):1-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29623248 ) ) [47] => SimpleXMLElement Object ( [Citation] => Immunol Rev. 2019 Jan;287(1):103-120 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30565240 ) ) [48] => SimpleXMLElement Object ( [Citation] => Sci Immunol. 2019 Apr 12;4(34):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30979797 ) ) [49] => SimpleXMLElement Object ( [Citation] => Medicine (Baltimore). 1981 Sep;60(5):355-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7024719 ) ) [50] => SimpleXMLElement Object ( [Citation] => Medicine (Baltimore). 1993 May;72(3):151-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8502168 ) ) [51] => SimpleXMLElement Object ( [Citation] => Respir Med. 1997 Aug;91(7):406-10 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9327041 ) ) [52] => SimpleXMLElement Object ( [Citation] => Am J Hum Genet. 1998 Dec;63(6):1675-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9837820 ) ) ) ) ) ) [6] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 30996332 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 04 [Day] => 29 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 11 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1529-2916 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 20 [Issue] => 5 [PubDate] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 05 ) ) [Title] => Nature immunology [ISOAbbreviation] => Nat Immunol ) [ArticleTitle] => CARD9 microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 559-570 ) [ELocationID] => 10.1038/s41590-019-0377-2 [Abstract] => SimpleXMLElement Object ( [AbstractText] => The C-type lectin receptor-Syk (spleen tyrosine kinase) adaptor CARD9 facilitates protective antifungal immunity within the central nervous system (CNS), as human deficiency in CARD9 causes susceptibility to fungus-specific, CNS-targeted infection. CARD9 promotes the recruitment of neutrophils to the fungus-infected CNS, which mediates fungal clearance. In the present study we investigated host and pathogen factors that promote protective neutrophil recruitment during invasion of the CNS by Candida albicans. The cytokine IL-1β served an essential function in CNS antifungal immunity by driving production of the chemokine CXCL1, which recruited neutrophils expressing the chemokine receptor CXCR2. Neutrophil-recruiting production of IL-1β and CXCL1 was induced in microglia by the fungus-secreted toxin Candidalysin, in a manner dependent on the kinase p38 and the transcription factor c-Fos. Notably, microglia relied on CARD9 for production of IL-1β, via both transcriptional regulation of Il1b and inflammasome activation, and of CXCL1 in the fungus-infected CNS. Microglia-specific Card9 deletion impaired the production of IL-1β and CXCL1 and neutrophil recruitment, and increased fungal proliferation in the CNS. Thus, an intricate network of host-pathogen interactions promotes antifungal immunity in the CNS; this is impaired in human deficiency in CARD9, which leads to fungal disease of the CNS. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Drummond [ForeName] => Rebecca A [Initials] => RA [Identifier] => http://orcid.org/0000-0001-5424-7074 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. r.drummond@bham.ac.uk. ) [1] => SimpleXMLElement Object ( [Affiliation] => Institute of Immunology & Immunotherapy, Institute of Microbiology & Infection, University of Birmingham, Birmingham, UK. r.drummond@bham.ac.uk. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Oikonomou [ForeName] => Vasileios [Initials] => V [Identifier] => http://orcid.org/0000-0002-7553-0159 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Zhai [ForeName] => Bing [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Dambuza [ForeName] => Ivy M [Initials] => IM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Medical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Schaefer [ForeName] => Brian C [Initials] => BC [Identifier] => http://orcid.org/0000-0001-8877-3507 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bohrer [ForeName] => Andrea C [Initials] => AC [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mayer-Barber [ForeName] => Katrin D [Initials] => KD [Identifier] => http://orcid.org/0000-0002-0311-3233 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lira [ForeName] => Sergio A [Initials] => SA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Iwakura [ForeName] => Yoichiro [Initials] => Y [Identifier] => http://orcid.org/0000-0002-9934-5775 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Filler [ForeName] => Scott G [Initials] => SG [Identifier] => http://orcid.org/0000-0001-7278-3700 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infectious Diseases, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Brown [ForeName] => Gordon D [Initials] => GD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Medical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hube [ForeName] => Bernhard [Initials] => B [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute Jena, Jena, Germany. ) [1] => SimpleXMLElement Object ( [Affiliation] => Friedrich Schiller University, Jena, Germany. ) ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Naglik [ForeName] => Julian R [Initials] => JR [Identifier] => http://orcid.org/0000-0002-8072-7917 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hohl [ForeName] => Tobias M [Initials] => TM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [Identifier] => http://orcid.org/0000-0003-4994-9500 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. lionakism@niaid.nih.gov. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => R01 DE026600 [Acronym] => DE [Agency] => NIDCR NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => R01 CA161373 [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) [2] => SimpleXMLElement Object ( [GrantID] => P30 CA008748 [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) [3] => SimpleXMLElement Object ( [GrantID] => R01 093808 [Acronym] => NH [Agency] => NIH HHS [Country] => United States ) [4] => SimpleXMLElement Object ( [GrantID] => R01CA161373 [Acronym] => NH [Agency] => NIH HHS [Country] => United States ) [5] => SimpleXMLElement Object ( [GrantID] => 102705/Z/13/Z [Acronym] => WT_ [Agency] => Wellcome Trust [Country] => United Kingdom ) [6] => SimpleXMLElement Object ( [GrantID] => MR/N006364/2 [Acronym] => MRC_ [Agency] => Medical Research Council [Country] => United Kingdom ) [7] => SimpleXMLElement Object ( [GrantID] => R01 DK110352 [Acronym] => DK [Agency] => NIDDK NIH HHS [Country] => United States ) [8] => SimpleXMLElement Object ( [GrantID] => R01 AI124566 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) [9] => SimpleXMLElement Object ( [GrantID] => R01AI124566 [Acronym] => NH [Agency] => NIH HHS [Country] => United States ) [10] => SimpleXMLElement Object ( [GrantID] => MR/N006364/1 [Acronym] => MRC_ [Agency] => Medical Research Council [Country] => United Kingdom ) [11] => SimpleXMLElement Object ( [GrantID] => R01 DE017088 [Acronym] => DE [Agency] => NIDCR NIH HHS [Country] => United States ) [12] => SimpleXMLElement Object ( [GrantID] => R01 AI093808 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) [13] => SimpleXMLElement Object ( [GrantID] => ZIA AI001175-01 [Acronym] => ImNIH [Agency] => Intramural NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Extramural [2] => Research Support, N.I.H., Intramural [3] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2019 [Month] => 04 [Day] => 17 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Nat Immunol [NlmUniqueID] => 100941354 [ISSNLinking] => 1529-2908 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CARD Signaling Adaptor Proteins ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Card9 protein, mouse ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Chemokine CXCL1 ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Cxcl1 protein, mouse ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Cytokines ) [5] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Inflammasomes ) [6] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Interleukin-1beta ) ) ) [CitationSubset] => IM [CommentsCorrectionsList] => SimpleXMLElement Object ( [CommentsCorrections] => SimpleXMLElement Object ( [@attributes] => Array ( [RefType] => CommentIn ) [RefSource] => Trends Immunol. 2019 Jul;40(7):555-556 [PMID] => 31133466 ) ) [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Brain [QualifierName] => Array ( [0] => immunology [1] => metabolism [2] => microbiology ) ) [2] => SimpleXMLElement Object ( [DescriptorName] => CARD Signaling Adaptor Proteins [QualifierName] => Array ( [0] => genetics [1] => immunology [2] => metabolism ) ) [3] => SimpleXMLElement Object ( [DescriptorName] => Candida albicans [QualifierName] => Array ( [0] => immunology [1] => physiology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Candidiasis [QualifierName] => Array ( [0] => genetics [1] => immunology [2] => microbiology ) ) [5] => SimpleXMLElement Object ( [DescriptorName] => Chemokine CXCL1 [QualifierName] => Array ( [0] => genetics [1] => immunology [2] => metabolism ) ) [6] => SimpleXMLElement Object ( [DescriptorName] => Cytokines [QualifierName] => Array ( [0] => genetics [1] => immunology [2] => metabolism ) ) [7] => SimpleXMLElement Object ( [DescriptorName] => Host-Pathogen Interactions [QualifierName] => immunology ) [8] => SimpleXMLElement Object ( [DescriptorName] => Inflammasomes [QualifierName] => Array ( [0] => genetics [1] => immunology [2] => metabolism ) ) [9] => SimpleXMLElement Object ( [DescriptorName] => Interleukin-1beta [QualifierName] => Array ( [0] => genetics [1] => immunology [2] => metabolism ) ) [10] => SimpleXMLElement Object ( [DescriptorName] => Mice, Knockout ) [11] => SimpleXMLElement Object ( [DescriptorName] => Mice, Transgenic ) [12] => SimpleXMLElement Object ( [DescriptorName] => Microglia [QualifierName] => Array ( [0] => immunology [1] => metabolism [2] => microbiology ) ) [13] => SimpleXMLElement Object ( [DescriptorName] => Neutrophil Infiltration [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [14] => SimpleXMLElement Object ( [DescriptorName] => Neutrophils [QualifierName] => Array ( [0] => immunology [1] => metabolism [2] => microbiology ) ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2018 [Month] => 05 [Day] => 25 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2019 [Month] => 03 [Day] => 12 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2019 [Month] => 4 [Day] => 19 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2019 [Month] => 4 [Day] => 19 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2019 [Month] => 4 [Day] => 30 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 30996332 [1] => 10.1038/s41590-019-0377-2 [2] => 10.1038/s41590-019-0377-2 [3] => PMC6494474 [4] => NIHMS1523856 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Nat Rev Microbiol. 2016 Mar;14(3):163-76 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26853116 ) ) [1] => SimpleXMLElement Object ( [Citation] => Immunity. 2003 Nov;19(5):749-58 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14614861 ) ) [2] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2013 Oct 31;369(18):1704-1714 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24131138 ) ) [3] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2012;8(8):e1002865 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22916017 ) ) [4] => SimpleXMLElement Object ( [Citation] => mBio. 2015 Jun 02;6(3):e00724 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26037125 ) ) [5] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2016 May 30;213(6):929-49 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27139491 ) ) [6] => SimpleXMLElement Object ( [Citation] => Hum Mol Genet. 2018 Jun 15;27(12):2076-2089 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29617956 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Pediatric Infect Dis Soc. 2017 Sep 1;6(3):e123-e133 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28903523 ) ) [8] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2006 Dec;74(12):6528-39 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16920786 ) ) [9] => SimpleXMLElement Object ( [Citation] => Cell. 2013 Dec 19;155(7):1596-609 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24360280 ) ) [10] => SimpleXMLElement Object ( [Citation] => Curr Fungal Infect Rep. 2018 Jun;12(2):92-97 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30393511 ) ) [11] => SimpleXMLElement Object ( [Citation] => Glia. 2006 Jan 1;53(1):24-31 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16086366 ) ) [12] => SimpleXMLElement Object ( [Citation] => Microbiol Mol Biol Rev. 2003 Sep;67(3):400-28, table of contents [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12966142 ) ) [13] => SimpleXMLElement Object ( [Citation] => Front Cell Infect Microbiol. 2016 Apr 05;6:39 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27092298 ) ) [14] => SimpleXMLElement Object ( [Citation] => Nat Rev Dis Primers. 2018 May 11;4:18026 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29749387 ) ) [15] => SimpleXMLElement Object ( [Citation] => Cell Host Microbe. 2018 Jan 10;23(1):121-133.e4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29290576 ) ) [16] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2010 Jan;11(1):63-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19915568 ) ) [17] => SimpleXMLElement Object ( [Citation] => Annu Rev Immunol. 2018 Apr 26;36:157-191 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29237128 ) ) [18] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2014 Feb;82(2):882-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24478101 ) ) [19] => SimpleXMLElement Object ( [Citation] => Blood. 2013 Mar 28;121(13):2385-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23335372 ) ) [20] => SimpleXMLElement Object ( [Citation] => J Neurosci. 2015 Jun 3;35(22):8411-22 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26041910 ) ) [21] => SimpleXMLElement Object ( [Citation] => Virulence. 2016 Oct 2;7(7):819-25 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27127904 ) ) [22] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2010 Sep 30;363(14):1303-12 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20879879 ) ) [23] => SimpleXMLElement Object ( [Citation] => Nat Neurosci. 2017 Jun;20(6):793-803 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28414331 ) ) [24] => SimpleXMLElement Object ( [Citation] => ALTEX. 2009;26(2):83-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19565166 ) ) [25] => SimpleXMLElement Object ( [Citation] => Cell Rep. 2017 May 9;19(6):1151-1164 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28494865 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [27] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2014 Nov;82(11):4508-17 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25114117 ) ) [28] => SimpleXMLElement Object ( [Citation] => Cell Host Microbe. 2015 Mar 11;17(3):357-368 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25704009 ) ) [29] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2018 Jan 22;86(2): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29109176 ) ) [30] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 2014 Jan 1;209(1):109-19 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23922372 ) ) [31] => SimpleXMLElement Object ( [Citation] => EMBO J. 2004 Apr 21;23(8):1845-56 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15071502 ) ) [32] => SimpleXMLElement Object ( [Citation] => Clin Immunol. 2018 Jun;191:21-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29307770 ) ) [33] => SimpleXMLElement Object ( [Citation] => J Immunol. 2009 Jan 15;182(2):1146-54 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19124758 ) ) [34] => SimpleXMLElement Object ( [Citation] => Nature. 2018 May;557(7707):724-728 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29769726 ) ) [35] => SimpleXMLElement Object ( [Citation] => J Immunol. 2001 Dec 1;167(11):6503-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11714818 ) ) [36] => SimpleXMLElement Object ( [Citation] => Brain Behav Immun. 2010 May;24(4):540-53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19932745 ) ) [37] => SimpleXMLElement Object ( [Citation] => Sci Transl Med. 2016 Jan 20;8(322):322ra10 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26791948 ) ) [38] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2016 Apr 01;7:11004 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27032818 ) ) [39] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2016 Sep 27;7:12874 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27670879 ) ) [40] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2009 Oct 29;361(18):1727-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19864672 ) ) [41] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2018 Oct 15;9(1):4260 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30323213 ) ) [42] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2016 Sep 15;12(9):e1005882 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27632536 ) ) [43] => SimpleXMLElement Object ( [Citation] => Blood. 2015 Jun 25;125(26):4085-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25852057 ) ) [44] => SimpleXMLElement Object ( [Citation] => J Neurochem. 2014 May;129(4):704-11 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24484406 ) ) [45] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2017 Mar 22;18(4):385-392 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28323268 ) ) [46] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Dec 17;11(12):e1005293 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26679537 ) ) [47] => SimpleXMLElement Object ( [Citation] => J Invest Dermatol. 2018 Mar;138(3):607-617 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29080677 ) ) [48] => SimpleXMLElement Object ( [Citation] => Nat Neurosci. 2013 Nov;16(11):1618-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24077561 ) ) [49] => SimpleXMLElement Object ( [Citation] => Cold Spring Harb Perspect Med. 2014 Jun 02;4(6): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24890837 ) ) [50] => SimpleXMLElement Object ( [Citation] => Sci Immunol. 2017 Nov 3;2(17): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29101209 ) ) [51] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2015 Jun;135(6):1558-68.e2 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25702837 ) ) [52] => SimpleXMLElement Object ( [Citation] => Cell Host Microbe. 2011 Dec 15;10(6):603-15 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22177564 ) ) [53] => SimpleXMLElement Object ( [Citation] => Nature. 2016 Apr 7;532(7597):64-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27027296 ) ) ) ) ) ) [7] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 30723080 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 12 [Day] => 16 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 02 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1528-0020 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 133 [Issue] => 18 [PubDate] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 05 [Day] => 02 ) ) [Title] => Blood [ISOAbbreviation] => Blood ) [ArticleTitle] => Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 1977-1988 ) [ELocationID] => 10.1182/blood-2018-11-886028 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Ras-related C3 botulinum toxin substrate 2 (RAC2), through interactions with reduced NAD phosphate oxidase component p67 , activates neutrophil superoxide production, whereas interactions with p21-activated kinase are necessary for fMLF-induced actin remodeling. We identified 3 patients with de novo RAC2[E62K] mutations resulting in severe T- and B-cell lymphopenia, myeloid dysfunction, and recurrent respiratory infections. Neutrophils from RAC2[E62K] patients exhibited excessive superoxide production, impaired fMLF-directed chemotaxis, and abnormal macropinocytosis. Cell lines transfected with RAC2[E62K] displayed characteristics of active guanosine triphosphate (GTP)-bound RAC2 including enhanced superoxide production and increased membrane ruffling. Biochemical studies demonstrated that RAC2[E62K] retains intrinsic GTP hydrolysis; however, GTPase-activating protein failed to accelerate hydrolysis resulting in prolonged active GTP-bound RAC2. Rac2 mice phenocopy the T- and B-cell lymphopenia, increased neutrophil F-actin, and excessive superoxide production seen in patients. This gain-of-function mutation highlights a specific, nonredundant role for RAC2 in hematopoietic cells that discriminates RAC2 from the related, ubiquitous RAC1. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hsu [ForeName] => Amy P [Initials] => AP [Identifier] => 0000-0001-6841-2122 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section and. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Donkó [ForeName] => Agnes [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Defenses Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Arrington [ForeName] => Megan E [Initials] => ME [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Chemistry, University of North Carolina (UNC), Chapel Hill, NC. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fink [ForeName] => Danielle [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Das [ForeName] => Arundhoti [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Escobedo [ForeName] => Omar [Initials] => O [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Defenses Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bonagura [ForeName] => Vincent [Initials] => V [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Cohen Children's Medical Center, New York, NY. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Szabolcs [ForeName] => Paul [Initials] => P [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Steinberg [ForeName] => Harry N [Initials] => HN [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => North Shore University Hospital, New Hyde Park, NY. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bergerson [ForeName] => Jenna [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section and. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Skoskiewicz [ForeName] => Amanda [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Makhija [ForeName] => Melanie [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Davis [ForeName] => Joie [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section and. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Foruraghi [ForeName] => Ladan [Initials] => L [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section and. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Palmer [ForeName] => Cindy [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section and. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fuleihan [ForeName] => Ramsay L [Initials] => RL [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Church [ForeName] => Joseph A [Initials] => JA [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Pediatric Allergy/Immunology, Children's Hospital Los Angeles, Los Angeles, CA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Clinical Pediatrics, Keck School of Medicine of USC, Los Angeles, CA; and. ) ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bhandoola [ForeName] => Avinash [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, LCIM, NIAID, NIH, Bethesda, MD. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Campbell [ForeName] => Sharon [Initials] => S [Identifier] => 0000-0003-0311-409X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biochemistry and Biophysics, UNC Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, NC. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Leto [ForeName] => Thomas L [Initials] => TL [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Defenses Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kuhns [ForeName] => Douglas B [Initials] => DB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section and. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => R21 AI105987 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => P01 CA203657 [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) [2] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001C [Acronym] => RC [Agency] => CCR NIH HHS [Country] => United States ) [3] => SimpleXMLElement Object ( [GrantID] => R01 DE017227 [Acronym] => DE [Agency] => NIDCR NIH HHS [Country] => United States ) [4] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001E [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Case Reports [1] => Journal Article [2] => Research Support, N.I.H., Extramural [3] => Research Support, N.I.H., Intramural ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2019 [Month] => 02 [Day] => 05 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Blood [NlmUniqueID] => 7603509 [ISSNLinking] => 0006-4971 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.6.1.- [NameOfSubstance] => rac2 GTP-binding protein ) [1] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.6.5.2 [NameOfSubstance] => rac GTP-Binding Proteins ) ) ) [CitationSubset] => Array ( [0] => AIM [1] => IM ) [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Adolescent ) [1] => SimpleXMLElement Object ( [DescriptorName] => Adult ) [2] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [3] => SimpleXMLElement Object ( [DescriptorName] => Child, Preschool ) [4] => SimpleXMLElement Object ( [DescriptorName] => Cytoskeleton [QualifierName] => pathology ) [5] => SimpleXMLElement Object ( [DescriptorName] => Female ) [6] => SimpleXMLElement Object ( [DescriptorName] => Gain of Function Mutation ) [7] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [8] => SimpleXMLElement Object ( [DescriptorName] => Immunologic Deficiency Syndromes [QualifierName] => genetics ) [9] => SimpleXMLElement Object ( [DescriptorName] => Infant ) [10] => SimpleXMLElement Object ( [DescriptorName] => Infant, Newborn ) [11] => SimpleXMLElement Object ( [DescriptorName] => Lymphopenia [QualifierName] => genetics ) [12] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [13] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred C57BL ) [14] => SimpleXMLElement Object ( [DescriptorName] => Pedigree ) [15] => SimpleXMLElement Object ( [DescriptorName] => rac GTP-Binding Proteins [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2018 [Month] => 11 [Day] => 14 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2019 [Month] => 01 [Day] => 29 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2019 [Month] => 2 [Day] => 7 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2019 [Month] => 12 [Day] => 18 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2019 [Month] => 2 [Day] => 7 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 30723080 [1] => S0006-4971(20)42591-1 [2] => 10.1182/blood-2018-11-886028 [3] => PMC6497516 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Science. 2003 Oct 17;302(5644):459-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14564011 ) ) [1] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 1998 Aug 21;273(34):21512-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9705280 ) ) [2] => SimpleXMLElement Object ( [Citation] => Oncogene. 1997 Jul 31;15(5):601-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9247314 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Cell Sci. 2004 Jan 15;117(Pt 2):243-55 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14676277 ) ) [4] => SimpleXMLElement Object ( [Citation] => Nat Med. 2017 Jun;23(6):703-713 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28481359 ) ) [5] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2008 Nov;9(11):1307-15 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18836449 ) ) [6] => SimpleXMLElement Object ( [Citation] => J Immunol. 2005 Apr 15;174(8):4613-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15814684 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2011 Feb;127(2):535-538.e1-2 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21167572 ) ) [8] => SimpleXMLElement Object ( [Citation] => Free Radic Biol Med. 2015 Feb;79:237-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25289457 ) ) [9] => SimpleXMLElement Object ( [Citation] => J Vis Exp. 2013 Jul 10;(77):e50586 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23892876 ) ) [10] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 1999 Aug 27;274(35):25051-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10455184 ) ) [11] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2015 May;135(5):1380-4.e1-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25512081 ) ) [12] => SimpleXMLElement Object ( [Citation] => PLoS Biol. 2018 Jul 9;16(7):e2005380 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29985916 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Mol Biol. 2008 May 23;379(1):51-63 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18440551 ) ) [14] => SimpleXMLElement Object ( [Citation] => Clin Immunol. 2011 Nov;141(2):128-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21763205 ) ) [15] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 1997 Jul 25;272(30):18834-41 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9228059 ) ) [16] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2011 Dec;41(12):3423-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21969276 ) ) [17] => SimpleXMLElement Object ( [Citation] => JAMA. 2009 Dec 9;302(22):2465-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19996402 ) ) [18] => SimpleXMLElement Object ( [Citation] => Exp Cell Res. 2013 Sep 10;319(15):2375-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23850828 ) ) [19] => SimpleXMLElement Object ( [Citation] => Mol Biol Cell. 2004 Aug;15(8):3509-19 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15169870 ) ) [20] => SimpleXMLElement Object ( [Citation] => J Immunol. 2002 Nov 1;169(9):5043-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12391220 ) ) [21] => SimpleXMLElement Object ( [Citation] => FEBS Lett. 2003 Dec 18;555(3):556-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14675773 ) ) [22] => SimpleXMLElement Object ( [Citation] => Am J Hum Genet. 2018 Feb 1;102(2):309-320 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29394990 ) ) [23] => SimpleXMLElement Object ( [Citation] => Immunity. 1999 Feb;10(2):183-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10072071 ) ) [24] => SimpleXMLElement Object ( [Citation] => Science. 1991 Dec 6;254(5037):1512-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1660188 ) ) [25] => SimpleXMLElement Object ( [Citation] => Mol Cell. 2000 Dec;6(6):1449-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11163217 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Pediatr Hematol Oncol. 2002 Dec;24(9):791-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12468931 ) ) [27] => SimpleXMLElement Object ( [Citation] => Sci Rep. 2017 Sep 20;7(1):11978 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28931895 ) ) [28] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2015 Oct 14;6:8623 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26465210 ) ) [29] => SimpleXMLElement Object ( [Citation] => Blood. 2018 Nov 29;132(22):2362-2374 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30254128 ) ) [30] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2017 Mar 17;292(11):4446-4456 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28154176 ) ) [31] => SimpleXMLElement Object ( [Citation] => Biochemistry. 1997 Jan 21;36(3):626-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9012677 ) ) [32] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [33] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 1995 Oct 13;270(41):23934-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7592586 ) ) [34] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4654-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10758162 ) ) [35] => SimpleXMLElement Object ( [Citation] => Blood. 2009 Apr 23;113(17):3990-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19088377 ) ) [36] => SimpleXMLElement Object ( [Citation] => Sci Rep. 2013;3:2385 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23924974 ) ) [37] => SimpleXMLElement Object ( [Citation] => J Immunol. 2001 Jan 15;166(2):1223-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11145705 ) ) [38] => SimpleXMLElement Object ( [Citation] => Nat Cell Biol. 2008 Nov;10(11):1356-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18931661 ) ) [39] => SimpleXMLElement Object ( [Citation] => Curr Biol. 1997 Mar 1;7(3):202-10 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9395435 ) ) [40] => SimpleXMLElement Object ( [Citation] => Blood. 2000 Sep 1;96(5):1646-54 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10961859 ) ) [41] => SimpleXMLElement Object ( [Citation] => Nat Genet. 2012 Sep;44(9):1006-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22842228 ) ) [42] => SimpleXMLElement Object ( [Citation] => J Cell Biol. 2007 Oct 22;179(2):239-45 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17954607 ) ) [43] => SimpleXMLElement Object ( [Citation] => Methods Mol Biol. 2014;1124:79-88 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24504947 ) ) [44] => SimpleXMLElement Object ( [Citation] => J Cell Sci. 2016 Apr 1;129(7):1287-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26985062 ) ) [45] => SimpleXMLElement Object ( [Citation] => Nat Genet. 2015 Nov;47(11):1334-40 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26457648 ) ) ) ) ) ) [8] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 29890237 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 09 [Day] => 16 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 09 [Day] => 16 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1097-6825 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 142 [Issue] => 4 [PubDate] => SimpleXMLElement Object ( [Year] => 2018 [Month] => 10 ) ) [Title] => The Journal of allergy and clinical immunology [ISOAbbreviation] => J Allergy Clin Immunol ) [ArticleTitle] => GM-CSF therapy in human caspase recruitment domain-containing protein 9 deficiency. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 1334-1338.e5 ) [ELocationID] => Array ( [0] => S0091-6749(18)30846-7 [1] => 10.1016/j.jaci.2018.05.025 ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Drummond [ForeName] => Rebecca A [Initials] => RA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Md. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Zahra [ForeName] => Fatema Tuz [Initials] => FT [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Tex. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Natarajan [ForeName] => Mukil [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Md. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Md. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hsu [ForeName] => Amy P [Initials] => AP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Md. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Wheat [ForeName] => L Joseph [Initials] => LJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => MiraVista Diagnostics, Indianapolis, Ind. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Gavino [ForeName] => Christina [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Disease Susceptibility Program, McGill University Health Centre (MUHC) and Research Institute-MUHC, Montreal, Quebec, Canada. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Vinh [ForeName] => Donald C [Initials] => DC [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Disease Susceptibility Program, McGill University Health Centre (MUHC) and Research Institute-MUHC, Montreal, Quebec, Canada. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Md. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mikelis [ForeName] => Constantinos M [Initials] => CM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Tex. Electronic address: constantinos.mikelis@ttuhsc.edu. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: lionakism@mail.nih.gov. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Case Reports [1] => Letter [2] => Research Support, N.I.H., Intramural ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2018 [Month] => 06 [Day] => 08 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Allergy Clin Immunol [NlmUniqueID] => 1275002 [ISSNLinking] => 0091-6749 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CARD Signaling Adaptor Proteins ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CARD9 protein, human ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 83869-56-1 [NameOfSubstance] => Granulocyte-Macrophage Colony-Stimulating Factor ) ) ) [CitationSubset] => Array ( [0] => AIM [1] => IM ) [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => CARD Signaling Adaptor Proteins [QualifierName] => Array ( [0] => deficiency [1] => genetics ) ) [2] => SimpleXMLElement Object ( [DescriptorName] => Candida albicans ) [3] => SimpleXMLElement Object ( [DescriptorName] => Candidiasis [QualifierName] => Array ( [0] => drug therapy [1] => microbiology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Female ) [5] => SimpleXMLElement Object ( [DescriptorName] => Granulocyte-Macrophage Colony-Stimulating Factor [QualifierName] => therapeutic use ) [6] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [7] => SimpleXMLElement Object ( [DescriptorName] => Immunologic Deficiency Syndromes [QualifierName] => Array ( [0] => drug therapy [1] => microbiology ) ) [8] => SimpleXMLElement Object ( [DescriptorName] => Meningoencephalitis [QualifierName] => Array ( [0] => drug therapy [1] => microbiology ) ) [9] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred C57BL ) [10] => SimpleXMLElement Object ( [DescriptorName] => Mice, Knockout ) [11] => SimpleXMLElement Object ( [DescriptorName] => Neutropenia [QualifierName] => Array ( [0] => drug therapy [1] => microbiology ) ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2017 [Month] => 07 [Day] => 26 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2018 [Month] => 03 [Day] => 30 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2018 [Month] => 05 [Day] => 18 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2018 [Month] => 6 [Day] => 12 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2019 [Month] => 9 [Day] => 17 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2018 [Month] => 6 [Day] => 12 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 29890237 [1] => S0091-6749(18)30846-7 [2] => 10.1016/j.jaci.2018.05.025 ) ) ) ) [9] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 29415879 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 10 [Day] => 28 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 10 [Day] => 28 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic-eCollection ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2379-3708 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 3 [Issue] => 3 [PubDate] => SimpleXMLElement Object ( [Year] => 2018 [Month] => 02 [Day] => 08 ) ) [Title] => JCI insight [ISOAbbreviation] => JCI Insight ) [ArticleTitle] => The homozygous CX3CR1-M280 mutation impairs human monocyte survival. [ELocationID] => Array ( [0] => 10.1172/jci.insight.95417 [1] => 95417 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Several reports have demonstrated that mouse Cx3cr1 signaling promotes monocyte/macrophage survival. In agreement, we previously found that, in a mouse model of systemic candidiasis, genetic deficiency of Cx3cr1 resulted in increased mortality and impaired tissue fungal clearance associated with decreased macrophage survival. We translated this finding by showing that the dysfunctional CX3CR1 variant CX3CR1-M280 was associated with increased risk and worse outcome of human systemic candidiasis. However, the impact of this mutation on human monocyte/macrophage survival is poorly understood. Herein, we hypothesized that CX3CR1-M280 impairs human monocyte survival. We identified WT (CX3CR1-WT/WT), CX3CR1-WT/M280 heterozygous, and CX3CR1-M280/M280 homozygous healthy donors of European descent, and we show that CX3CL1 rescues serum starvation-induced cell death in CX3CR1-WT/WT and CX3CR1-WT/M280 but not in CX3CR1-M280/M280 monocytes. CX3CL1-induced survival of CX3CR1-WT/WT monocytes is mediated via AKT and ERK activation, which are both impaired in CX3CR1-M280/M280 monocytes, associated with decreased blood monocyte counts in CX3CR1-M280/M280 donors at steady state. Instead, CX3CR1-M280/M280 does not affect monocyte CX3CR1 surface expression or innate immune effector functions. Together, we show that homozygocity of the M280 polymorphism in CX3CR1 is a potentially novel population-based genetic factor that influences human monocyte signaling. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Collar [ForeName] => Amanda L [Initials] => AL [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID) , and. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID) , and. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => O'Hayre [ForeName] => Morgan [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research (NIDCR), NIH, Bethesda, Maryland, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sajib [ForeName] => Md Sanaullah [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hoffman [ForeName] => Kevin W [Initials] => KW [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Singh [ForeName] => Satya P [Initials] => SP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular Immunology (LMI), NIAID, NIH, Bethesda, Maryland, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mourad [ForeName] => Ahmad [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infectious Diseases, Duke University School of Medicine, Durham, North Carolina, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Johnson [ForeName] => Melissa D [Initials] => MD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infectious Diseases, Duke University School of Medicine, Durham, North Carolina, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ferre [ForeName] => Elise Mn [Initials] => EM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID) , and. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Farber [ForeName] => Joshua M [Initials] => JM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular Immunology (LMI), NIAID, NIH, Bethesda, Maryland, USA. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lim [ForeName] => Jean K [Initials] => JK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mikelis [ForeName] => Constantinos M [Initials] => CM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Gutkind [ForeName] => J Silvio [Initials] => JS [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research (NIDCR), NIH, Bethesda, Maryland, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology, UCSD, San Diego, California, USA. ) ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID) , and. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Intramural ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2018 [Month] => 02 [Day] => 08 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => JCI Insight [NlmUniqueID] => 101676073 [ISSNLinking] => 2379-3708 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CX3C Chemokine Receptor 1 ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CX3CL1 protein, human ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CX3CR1 protein, human ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Chemokine CX3CL1 ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Culture Media, Serum-Free ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Apoptosis [QualifierName] => immunology ) [1] => SimpleXMLElement Object ( [DescriptorName] => CX3C Chemokine Receptor 1 [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [2] => SimpleXMLElement Object ( [DescriptorName] => Cell Culture Techniques ) [3] => SimpleXMLElement Object ( [DescriptorName] => Cell Survival [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Cells, Cultured ) [5] => SimpleXMLElement Object ( [DescriptorName] => Chemokine CX3CL1 [QualifierName] => Array ( [0] => immunology [1] => metabolism ) ) [6] => SimpleXMLElement Object ( [DescriptorName] => Culture Media, Serum-Free ) [7] => SimpleXMLElement Object ( [DescriptorName] => Healthy Volunteers ) [8] => SimpleXMLElement Object ( [DescriptorName] => Homozygote ) [9] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [10] => SimpleXMLElement Object ( [DescriptorName] => Monocytes [QualifierName] => physiology ) [11] => SimpleXMLElement Object ( [DescriptorName] => Mutation ) ) ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Chemokines [1] => Immunology [2] => Infectious disease [3] => Monocytes ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2017 [Month] => 05 [Day] => 30 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2017 [Month] => 12 [Day] => 29 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2018 [Month] => 2 [Day] => 9 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2019 [Month] => 10 [Day] => 29 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2018 [Month] => 2 [Day] => 9 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 29415879 [1] => 95417 [2] => 10.1172/jci.insight.95417 [3] => PMC5821174 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Circ Res. 2001 Aug 31;89(5):401-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11532900 ) ) [1] => SimpleXMLElement Object ( [Citation] => Med Mycol. 2014 Aug;52(6):555-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25023483 ) ) [2] => SimpleXMLElement Object ( [Citation] => Hepatology. 2010 Nov;52(5):1769-82 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21038415 ) ) [3] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2003 Jan;33(1):53-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12594832 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2007 Oct;117(10):2920-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17909628 ) ) [5] => SimpleXMLElement Object ( [Citation] => Mol Cancer. 2013 Nov 18;12(1):141 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24245985 ) ) [6] => SimpleXMLElement Object ( [Citation] => J Immunol. 2015 Sep 15;195(6):2797-805 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26254342 ) ) [7] => SimpleXMLElement Object ( [Citation] => Cell Mol Immunol. 2015 Nov;12(6):669-80 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25502213 ) ) [8] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2014 Mar 27;370(13):1198-208 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24670166 ) ) [9] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2003 Apr;111(8):1241-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12697743 ) ) [10] => SimpleXMLElement Object ( [Citation] => J Immunol. 2000 Jul 1;165(1):397-403 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10861077 ) ) [11] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2011 Dec;121(12):4787-95 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22045567 ) ) [12] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 2006 Jan;316(1):356-63 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16166268 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2013 Dec;123(12):5035-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24177428 ) ) [14] => SimpleXMLElement Object ( [Citation] => Science. 2000 Mar 24;287(5461):2274-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10731151 ) ) [15] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2011 May;41(5):1256-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21425158 ) ) [16] => SimpleXMLElement Object ( [Citation] => JCI Insight. 2017 Jun 2;2(11):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28570272 ) ) [17] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):847-53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15681302 ) ) [18] => SimpleXMLElement Object ( [Citation] => Blood. 2009 Jan 22;113(4):963-72 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18971423 ) ) [19] => SimpleXMLElement Object ( [Citation] => J Leukoc Biol. 2006 Nov;80(5):1156-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17056766 ) ) [20] => SimpleXMLElement Object ( [Citation] => Blood. 2011 Sep 8;118(10):2653-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21670465 ) ) [21] => SimpleXMLElement Object ( [Citation] => Blood. 2001 Apr 1;97(7):1925-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11264153 ) ) [22] => SimpleXMLElement Object ( [Citation] => Blood. 2011 Nov 24;118(22):e156-67 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21951685 ) ) [23] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2011 Oct;41(10):2915-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21695694 ) ) [24] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [25] => SimpleXMLElement Object ( [Citation] => Blood. 2011 Nov 3;118(18):4957-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21890643 ) ) [26] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):589-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22247260 ) ) [27] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2015 Oct;15(10):630-42 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26388329 ) ) [28] => SimpleXMLElement Object ( [Citation] => Pharmacol Rev. 2013 Nov 11;66(1):1-79 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24218476 ) ) [29] => SimpleXMLElement Object ( [Citation] => Circulation. 2006 Aug 22;114(8):807-19 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16908772 ) ) [30] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2297-305 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23887641 ) ) [31] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2011 Jul 14;365(2):127-38 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21524210 ) ) [32] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2015 Jan 9;290(2):827-40 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25425646 ) ) [33] => SimpleXMLElement Object ( [Citation] => Cardiovasc Res. 2010 Mar 1;85(4):825-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19840952 ) ) [34] => SimpleXMLElement Object ( [Citation] => Oncogene. 2003 Dec 8;22(56):8983-98 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14663477 ) ) [35] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Dec 17;11(12):e1005293 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26679537 ) ) [36] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2016 Feb;17(2):159-68 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26642357 ) ) [37] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2554-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25359863 ) ) [38] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2004 May 7;279(19):19649-57 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14990582 ) ) ) ) ) ) [10] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 28887465 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 06 [Day] => 11 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 06 [Day] => 13 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2045-2322 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 7 [Issue] => 1 [PubDate] => SimpleXMLElement Object ( [Year] => 2017 [Month] => 09 [Day] => 08 ) ) [Title] => Scientific reports [ISOAbbreviation] => Sci Rep ) [ArticleTitle] => Host immune status-specific production of gliotoxin and bis-methyl-gliotoxin during invasive aspergillosis in mice. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 10977 ) [ELocationID] => 10.1038/s41598-017-10888-9 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT's role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A. fumigatus-infected chronic granulomatous disease (CGD), hydrocortisone-treated, and neutropenic mice. We harvested lungs for assessment of fungal burden, histology and GT/bmGT biosynthetic genes' mRNA induction. GT levels were higher in neutropenic versus CGD or steroid-treated lungs. bmGT was persistently detected only in CGD lungs. GT, but not bmGT, was detected in 71% of sera and 50% of BALF of neutropenic mice; neither was detected in serum/BALF of CGD or steroid-treated mice. Enrichment of GT in Aspergillus-infected neutropenic lung correlated with fungal burden and hyphal length but not induction of GT biosynthetic genes. In summary, GT is detectable in mouse lungs, serum and BALF during neutropenic IA, suggesting that GT may be useful to diagnose IA in neutropenic patients. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sugui [ForeName] => Janyce A [Initials] => JA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Microbiology Section, Laboratory of Clinical Immunology & Microbiology (LCIM), National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rose [ForeName] => Stacey R [Initials] => SR [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, LCIM, NIAID, NIH, Bethesda, MD, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Division of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA. ) ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nardone [ForeName] => Glenn [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Research Technology Branch, NIH, Rockville, MD, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, LCIM, NIAID, NIH, Bethesda, MD, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lee [ForeName] => Chyi-Chia R [Initials] => CR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kwon-Chung [ForeName] => Kyung J [Initials] => KJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular Microbiology Section, Laboratory of Clinical Immunology & Microbiology (LCIM), National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. jkchung@niaid.nih.gov. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, LCIM, NIAID, NIH, Bethesda, MD, USA. lionakism@mail.nih.gov. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Intramural ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2017 [Month] => 09 [Day] => 08 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => Sci Rep [NlmUniqueID] => 101563288 [ISSNLinking] => 2045-2322 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Steroids ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 67-99-2 [NameOfSubstance] => Gliotoxin ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Aspergillosis [QualifierName] => Array ( [0] => etiology [1] => metabolism [2] => mortality [3] => pathology ) ) [2] => SimpleXMLElement Object ( [DescriptorName] => Aspergillus [QualifierName] => immunology ) [3] => SimpleXMLElement Object ( [DescriptorName] => Disease Models, Animal ) [4] => SimpleXMLElement Object ( [DescriptorName] => Gliotoxin [QualifierName] => biosynthesis ) [5] => SimpleXMLElement Object ( [DescriptorName] => Granulomatous Disease, Chronic [QualifierName] => complications ) [6] => SimpleXMLElement Object ( [DescriptorName] => Host-Pathogen Interactions [QualifierName] => immunology ) [7] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [8] => SimpleXMLElement Object ( [DescriptorName] => Mice, Knockout ) [9] => SimpleXMLElement Object ( [DescriptorName] => Neutropenia [QualifierName] => complications ) [10] => SimpleXMLElement Object ( [DescriptorName] => Pulmonary Aspergillosis [QualifierName] => Array ( [0] => etiology [1] => metabolism [2] => mortality [3] => pathology ) ) [11] => SimpleXMLElement Object ( [DescriptorName] => Risk Factors ) [12] => SimpleXMLElement Object ( [DescriptorName] => Steroids [QualifierName] => pharmacology ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2017 [Month] => 04 [Day] => 24 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2017 [Month] => 08 [Day] => 14 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2017 [Month] => 9 [Day] => 10 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2017 [Month] => 9 [Day] => 10 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2019 [Month] => 6 [Day] => 14 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 28887465 [1] => 10.1038/s41598-017-10888-9 [2] => 10.1038/s41598-017-10888-9 [3] => PMC5591180 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2008 Jun 15;46(12):1813-21 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18462102 ) ) [1] => SimpleXMLElement Object ( [Citation] => Int J Med Microbiol. 2008 Apr;298(3-4):319-27 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17574915 ) ) [2] => SimpleXMLElement Object ( [Citation] => BMC Infect Dis. 2013 Jun 01;13:255 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23725402 ) ) [3] => SimpleXMLElement Object ( [Citation] => MBio. 2011 Nov 22;2(6):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22108383 ) ) [4] => SimpleXMLElement Object ( [Citation] => Haematologica. 2006 Jul;91(7):986-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16757415 ) ) [5] => SimpleXMLElement Object ( [Citation] => J Bacteriol. 1998 Jun;180(12):3031-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9620950 ) ) [6] => SimpleXMLElement Object ( [Citation] => Eur J Clin Invest. 2015 Jun;45(6):646-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25851301 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Immunol. 2009 Apr 1;182(7):4306-12 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19299730 ) ) [8] => SimpleXMLElement Object ( [Citation] => Med Mycol. 2009;47 Suppl 1:S271-81 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18654923 ) ) [9] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2004 Jun;72(6):3373-82 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15155643 ) ) [10] => SimpleXMLElement Object ( [Citation] => Am J Respir Crit Care Med. 1995 Sep;152(3):1079-86 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7663787 ) ) [11] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2010 Jun 15;50(12):1559-67 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20450350 ) ) [12] => SimpleXMLElement Object ( [Citation] => Environ Microbiol. 2016 Apr;18(4):1096-109 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26443473 ) ) [13] => SimpleXMLElement Object ( [Citation] => Semin Respir Crit Care Med. 2015 Oct;36(5):662-72 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26398533 ) ) [14] => SimpleXMLElement Object ( [Citation] => J Clin Microbiol. 2005 Dec;43(12):6120-2 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16333108 ) ) [15] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2005 Jun 15;40(12):1762-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15909264 ) ) [16] => SimpleXMLElement Object ( [Citation] => Clin Microbiol Rev. 2014 Jul;27(3):490-526 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24982319 ) ) [17] => SimpleXMLElement Object ( [Citation] => J Toxicol Environ Health A. 2003 Aug 8;66(15):1441-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12857634 ) ) [18] => SimpleXMLElement Object ( [Citation] => PLoS One. 2012;7(8):e43347 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22905261 ) ) [19] => SimpleXMLElement Object ( [Citation] => FEMS Yeast Res. 2007 Sep;7(6):986-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17537180 ) ) [20] => SimpleXMLElement Object ( [Citation] => Eukaryot Cell. 2007 Sep;6(9):1562-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17601876 ) ) [21] => SimpleXMLElement Object ( [Citation] => Appl Microbiol Biotechnol. 2016 Mar;100(5):2327-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26678078 ) ) [22] => SimpleXMLElement Object ( [Citation] => Diagn Microbiol Infect Dis. 2012 May;73(1):57-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22480566 ) ) [23] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 2009 Aug 15;200(4):647-56 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19591573 ) ) [24] => SimpleXMLElement Object ( [Citation] => Lancet. 2003 Nov 29;362(9398):1828-38 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14654323 ) ) [25] => SimpleXMLElement Object ( [Citation] => Am J Med. 2012 Jan;125(1 Suppl):S14-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22196205 ) ) [26] => SimpleXMLElement Object ( [Citation] => Clin Exp Allergy. 2000 Apr;30(4):476-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10718844 ) ) [27] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2005 Sep 1;41(5):654-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16080087 ) ) [28] => SimpleXMLElement Object ( [Citation] => J Infect. 2014 Sep;69(3):278-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24797077 ) ) [29] => SimpleXMLElement Object ( [Citation] => Chem Biol. 2014 Aug 14;21(8):999-1012 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25126990 ) ) [30] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2005 Jan;73(1):235-44 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15618159 ) ) [31] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2005 Jan;73(1):635-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15618207 ) ) [32] => SimpleXMLElement Object ( [Citation] => J Exp Med. 1996 Apr 1;183(4):1829-40 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8666939 ) ) [33] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 2008 Feb 1;197(3):479-86 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18199036 ) ) [34] => SimpleXMLElement Object ( [Citation] => PLoS One. 2008 Jul 09;3(7):e2655 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18648542 ) ) ) ) ) ) [11] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => PubMed-not-MEDLINE [Owner] => NLM ) [PMID] => 28769929 [DateRevised] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 11 [Day] => 20 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic-eCollection ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1664-3224 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Print ) [Volume] => 8 [PubDate] => SimpleXMLElement Object ( [Year] => 2017 ) ) [Title] => Frontiers in immunology [ISOAbbreviation] => Front Immunol ) [ArticleTitle] => Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 820 ) [ELocationID] => 10.3389/fimmu.2017.00820 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator () mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Given the common clinical features between patients with and GOF mutations, we sought to determine whether APECED patients also exhibit increased levels of STAT1 protein and phosphorylation in CD14 monocytes. We obtained peripheral blood mononuclear cells from 8 APECED patients and 13 healthy controls and assessed the levels of STAT1 protein and STAT1 tyrosine phosphorylation at rest and following IFN-γ stimulation, as well as the levels of mRNA. The mean STAT1 protein levels in CD14 monocytes exhibited a ~20% significant decrease in APECED patients both at rest and after IFN-γ stimulation relative to that of healthy donors. Similarly, the mean peak value of IFN-γ-induced pSTAT1 level was ~20% significantly lower in APECED patients compared to that in healthy controls. The decrease in STAT1 and peak pSTAT1 in APECED patients was not accompanied by decreased mRNA or anti-IFN-γ autoantibodies; instead, it correlated with the presence of autoantibodies to type I IFN and decreased monocyte surface expression of IFN-γ receptor 2. Our data show that, in contrast to patients with GOF mutations, APECED patients show a moderate but consistent and significant decrease in total STAT1 protein levels, associated with lower peak levels of pSTAT1 molecules after IFN-γ stimulation. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Zimmerman [ForeName] => Ofer [Initials] => O [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rosen [ForeName] => Lindsey B [Initials] => LB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ferre [ForeName] => Elise M N [Initials] => EMN [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Natarajan [ForeName] => Mukil [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => van de Veerdonk [ForeName] => Frank [Initials] => F [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Internal Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RILMS), Nijmegen, Netherlands. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2017 [Month] => 07 [Day] => 14 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => Switzerland [MedlineTA] => Front Immunol [NlmUniqueID] => 101560960 [ISSNLinking] => 1664-3224 ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => AIRE [1] => APECED [2] => CD14+ monocytes [3] => IFN-γ [4] => STAT1 [5] => chronic mucocutaneous candidiasis [6] => phosphorylation ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2017 [Month] => 05 [Day] => 15 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2017 [Month] => 06 [Day] => 29 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2017 [Month] => 8 [Day] => 4 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2017 [Month] => 8 [Day] => 5 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2017 [Month] => 8 [Day] => 5 [Hour] => 6 [Minute] => 1 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 28769929 [1] => 10.3389/fimmu.2017.00820 [2] => PMC5509791 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Blood. 2016 Jun 23;127(25):3154-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27114460 ) ) [1] => SimpleXMLElement Object ( [Citation] => Blood. 2010 Dec 23;116(26):5895-906 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20841510 ) ) [2] => SimpleXMLElement Object ( [Citation] => JCI Insight. 2016 Aug 18;1(13):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27588307 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2006 Aug;91(8):2843-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16684821 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2013 Jun;131(6):1611-23 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23534974 ) ) [5] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 1990 Jun 28;322(26):1829-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2348835 ) ) [6] => SimpleXMLElement Object ( [Citation] => Science. 2008 Aug 8;321(5890):843-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18687966 ) ) [7] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10626-31 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9724754 ) ) [8] => SimpleXMLElement Object ( [Citation] => Nat Genet. 1997 Dec;17(4):399-403 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9398840 ) ) [9] => SimpleXMLElement Object ( [Citation] => J Intern Med. 2007 Jun;261(6):605-10 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17547716 ) ) [10] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2011 Jul 7;365(1):54-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21714643 ) ) [11] => SimpleXMLElement Object ( [Citation] => Front Immunol. 2017 Mar 13;8:274 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28348565 ) ) [12] => SimpleXMLElement Object ( [Citation] => J Leukoc Biol. 2001 Dec;70(6):950-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11739558 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2010 Feb 15;207(2):291-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20123958 ) ) [14] => SimpleXMLElement Object ( [Citation] => Immunity. 2016 May 17;44(5):1102-13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27130899 ) ) [15] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2016 Jul;138(1):297-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26948078 ) ) [16] => SimpleXMLElement Object ( [Citation] => JAKSTAT. 2013 Jul 1;2(3):e23931 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24069549 ) ) [17] => SimpleXMLElement Object ( [Citation] => Immunity. 2016 Nov 15;45(5):999-1012 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27851927 ) ) [18] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2007 Feb;92(2):595-603 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17118990 ) ) [19] => SimpleXMLElement Object ( [Citation] => Cell. 2016 Jul 28;166(3):582-95 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27426947 ) ) [20] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2017 May;139(5):1629-1640.e2 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28139313 ) ) [21] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2008 May;118(5):1712-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18414681 ) ) [22] => SimpleXMLElement Object ( [Citation] => Annu Rev Immunol. 2009;27:287-312 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19302042 ) ) [23] => SimpleXMLElement Object ( [Citation] => Mol Immunol. 2008 Apr;45(7):1847-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18083234 ) ) [24] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2011 Aug 1;208(8):1635-48 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21727188 ) ) [25] => SimpleXMLElement Object ( [Citation] => Science. 2002 Nov 15;298(5597):1395-401 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12376594 ) ) [26] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2009 Sep 15;49(6):e62-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19681704 ) ) [27] => SimpleXMLElement Object ( [Citation] => Immunity. 2015 Jun 16;42(6):1185-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26084028 ) ) [28] => SimpleXMLElement Object ( [Citation] => J Clin Immunol. 2012 Apr;32(2):238-45 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22170314 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2013 Jun;131(6):1624-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23541320 ) ) [30] => SimpleXMLElement Object ( [Citation] => Curr Opin Immunol. 2012 Aug;24(4):364-78 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22651901 ) ) [31] => SimpleXMLElement Object ( [Citation] => Cell. 1994 Mar 11;76(5):821-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7510216 ) ) [32] => SimpleXMLElement Object ( [Citation] => Science. 2015 May 1;348(6234):589-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25791085 ) ) [33] => SimpleXMLElement Object ( [Citation] => Blood. 2008 Oct 1;112(7):2657-66 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18606876 ) ) [34] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2010 Feb 15;207(2):299-308 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20123959 ) ) [35] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2017 Aug;140(2):553-564.e4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28069426 ) ) [36] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2001 Oct;86(10):4747-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11600535 ) ) ) ) ) ) [12] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 27993850 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2017 [Month] => 09 [Day] => 12 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 12 [Day] => 09 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic-Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1098-6596 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 61 [Issue] => 3 [PubDate] => SimpleXMLElement Object ( [Year] => 2017 [Month] => 03 ) ) [Title] => Antimicrobial agents and chemotherapy [ISOAbbreviation] => Antimicrob Agents Chemother ) [ArticleTitle] => Pharmacological Blockade of the Chemokine Receptor CCR1 Protects Mice from Systemic Candidiasis of Hematogenous Origin. [ELocationID] => Array ( [0] => e02365-16 [1] => 10.1128/AAC.02365-16 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Systemic candidiasis is a leading cause of nosocomial bloodstream infection with a high mortality rate despite treatment. Immune-based strategies are needed to improve outcomes. We previously reported that genetic deficiency in the chemokine receptor CCR1 improves survival and ameliorates tissue damage in -infected mice. Here, we found that treatment of immunocompetent -infected mice with the CCR1-selective antagonist BL5923 improves survival, decreases the kidney fungal burden, and protects from renal tissue injury. [CopyrightInformation] => Copyright © 2017 American Society for Microbiology. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA lionakism@mail.nih.gov dkontoyi@mdanderson.org. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Albert [ForeName] => Nathaniel D [Initials] => ND [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lee [ForeName] => Chyi-Chia R [Initials] => CR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Loetscher [ForeName] => Pius [Initials] => P [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Autoimmunity, Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kontoyiannis [ForeName] => Dimitrios P [Initials] => DP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA lionakism@mail.nih.gov dkontoyi@mdanderson.org. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2017 [Month] => 02 [Day] => 23 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Antimicrob Agents Chemother [NlmUniqueID] => 0315061 [ISSNLinking] => 0066-4804 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Ccr1 protein, mouse ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Piperazines ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, CCR1 ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Acute Kidney Injury [QualifierName] => Array ( [0] => immunology [1] => microbiology [2] => mortality [3] => prevention & control ) ) [1] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [2] => SimpleXMLElement Object ( [DescriptorName] => Candida albicans [QualifierName] => Array ( [0] => drug effects [1] => growth & development [2] => pathogenicity ) ) [3] => SimpleXMLElement Object ( [DescriptorName] => Candidiasis, Invasive [QualifierName] => Array ( [0] => drug therapy [1] => immunology [2] => microbiology [3] => mortality ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Drug Administration Schedule ) [5] => SimpleXMLElement Object ( [DescriptorName] => Female ) [6] => SimpleXMLElement Object ( [DescriptorName] => Gene Expression ) [7] => SimpleXMLElement Object ( [DescriptorName] => Hemorrhage [QualifierName] => Array ( [0] => immunology [1] => microbiology [2] => mortality [3] => prevention & control ) ) [8] => SimpleXMLElement Object ( [DescriptorName] => Host-Pathogen Interactions ) [9] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [10] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred C57BL ) [11] => SimpleXMLElement Object ( [DescriptorName] => Piperazines [QualifierName] => pharmacology ) [12] => SimpleXMLElement Object ( [DescriptorName] => Receptors, CCR1 [QualifierName] => Array ( [0] => antagonists & inhibitors [1] => genetics [2] => immunology ) ) [13] => SimpleXMLElement Object ( [DescriptorName] => Survival Analysis ) ) ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => CCR1 [1] => Candida [2] => candidiasis [3] => chemokine receptor ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2016 [Month] => 11 [Day] => 04 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2016 [Month] => 12 [Day] => 10 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2016 [Month] => 12 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2017 [Month] => 9 [Day] => 13 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2016 [Month] => 12 [Day] => 21 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 27993850 [1] => AAC.02365-16 [2] => 10.1128/AAC.02365-16 [3] => PMC5328547 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => J Immunol. 2014 Feb 1;192(3):886-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24367031 ) ) [1] => SimpleXMLElement Object ( [Citation] => Med Mycol. 2014 Aug;52(6):555-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25023483 ) ) [2] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2015 Oct 8;373(15):1445-56 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26444731 ) ) [3] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2014 Mar 27;370(13):1198-208 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24670166 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Immunol. 1997 Mar 1;158(5):2356-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9036985 ) ) [5] => SimpleXMLElement Object ( [Citation] => Am J Clin Pathol. 1981 Feb;75(2):190-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7468523 ) ) [6] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2013 Jan;9(1):e1003079 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23300452 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Antimicrob Chemother. 2015 Aug;70(8):2362-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25855759 ) ) [8] => SimpleXMLElement Object ( [Citation] => Infect Dis Clin North Am. 2016 Mar;30(1):103-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26739610 ) ) [9] => SimpleXMLElement Object ( [Citation] => Am J Pathol. 2007 Apr;170(4):1267-76 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17392166 ) ) [10] => SimpleXMLElement Object ( [Citation] => J Infect. 2016 Oct;73(4):369-74 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27452195 ) ) [11] => SimpleXMLElement Object ( [Citation] => Emerg Infect Dis. 2014 Nov;20(11):1833-40 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25340258 ) ) [12] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2008 Mar 1;46(5):696-702 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18230039 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [14] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2012;8(8):e1002865 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22916017 ) ) [15] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13063-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20616008 ) ) ) ) ) ) [13] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [IndexingMethod] => Curated [Owner] => NLM ) [PMID] => 27777981 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2018 [Month] => 10 [Day] => 02 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 10 [Day] => 08 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2379-3708 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Print ) [Volume] => 1 [Issue] => 17 [PubDate] => SimpleXMLElement Object ( [Year] => 2016 [Month] => Oct [Day] => 20 ) ) [Title] => JCI insight [ISOAbbreviation] => JCI Insight ) [ArticleTitle] => Extrapulmonary infection in patients with CARD9 deficiency. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => e89890 ) [ELocationID] => Array ( [0] => 10.1172/jci.insight.89890 [1] => 89890 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulmonary invasive aspergillosis at the ages of 8 and 18. One patient died at age 12 with progressive intra-abdominal aspergillosis. The other patient had presented with intra-abdominal candidiasis at age 9, and developed central nervous system aspergillosis at age 18 and intra-abdominal aspergillosis at age 25. Neither patient developed infection of the lungs. One patient had homozygous M1I (caspase recruitment domain family member 9) mutation, while the other had homozygous Q295X mutation; both patients lacked CARD9 protein expression. The patients had normal monocyte and Th17 cell numbers in peripheral blood, but their mononuclear cells exhibited impaired production of proinflammatory cytokines upon fungus-specific stimulation. Neutrophil phagocytosis, killing, and oxidative burst against were intact, but neither patient accumulated neutrophils in infected tissue despite normal neutrophil numbers in peripheral blood. The neutrophil tissue accumulation defect was not caused by defective neutrophil-intrinsic chemotaxis, indicating that production of neutrophil chemoattractants in extrapulmonary tissue is impaired in CARD9 deficiency. Taken together, our results show that CARD9 deficiency is the first known inherited or acquired condition that predisposes to extrapulmonary infection with sparing of the lungs, associated with impaired neutrophil recruitment to the site of infection. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rieber [ForeName] => Nikolaus [Initials] => N [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Infectious Diseases and Immunology, Department of Pediatrics I, University of Tübingen, Germany. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Pediatrics, Munich Schwabing Hospital, Munich Technical University, Munich, Germany. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Gazendam [ForeName] => Roel P [Initials] => RP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Freeman [ForeName] => Alexandra F [Initials] => AF [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hsu [ForeName] => Amy P [Initials] => AP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Collar [ForeName] => Amanda L [Initials] => AL [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sugui [ForeName] => Janyce A [Initials] => JA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Drummond [ForeName] => Rebecca A [Initials] => RA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rongkavilit [ForeName] => Chokechai [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Wayne State University and Children's Hospital of Michigan, Detroit, Michigan, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hoffman [ForeName] => Kevin [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Henderson [ForeName] => Carolyn [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Clark [ForeName] => Lily [Initials] => L [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mezger [ForeName] => Markus [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Diseases and Immunology, Department of Pediatrics I, University of Tübingen, Germany. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Engeholm [ForeName] => Maik [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research and Center for Neurology, Tübingen, Germany. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Schüle [ForeName] => Rebecca [Initials] => R [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research and Center for Neurology, Tübingen, Germany. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Neumayer [ForeName] => Bettina [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Pathology, University of Tübingen, Tübingen, Germany. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ebel [ForeName] => Frank [Initials] => F [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Max-von-Pettenkofer-Institute, Ludwig-Maximilians-University, Munich, Germany. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mikelis [ForeName] => Constantinos M [Initials] => CM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, USA. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pittaluga [ForeName] => Stefania [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Prasad [ForeName] => Vinod K [Initials] => VK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina, USA. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Singh [ForeName] => Anurag [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Diseases and Immunology, Department of Pediatrics I, University of Tübingen, Germany. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Milner [ForeName] => Joshua D [Initials] => JD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Williams [ForeName] => Kelli W [Initials] => KW [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lim [ForeName] => Jean K [Initials] => JK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Wayne State University and Children's Hospital of Michigan, Detroit, Michigan, USA. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kwon-Chung [ForeName] => Kyung J [Initials] => KJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) [26] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hartl [ForeName] => Dominik [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Infectious Diseases and Immunology, Department of Pediatrics I, University of Tübingen, Germany. ) ) [27] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kuijpers [ForeName] => Taco W [Initials] => TW [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ) ) [28] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => SimpleXMLElement Object ( [GrantID] => T32 AI007647 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Intramural [2] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2016 [Month] => 10 [Day] => 20 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => JCI Insight [NlmUniqueID] => 101676073 [ISSNLinking] => 2379-3708 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CARD Signaling Adaptor Proteins ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CARD9 protein, human ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Adolescent ) [1] => SimpleXMLElement Object ( [DescriptorName] => Adult ) [2] => SimpleXMLElement Object ( [DescriptorName] => Aspergillosis [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [3] => SimpleXMLElement Object ( [DescriptorName] => Aspergillus fumigatus ) [4] => SimpleXMLElement Object ( [DescriptorName] => CARD Signaling Adaptor Proteins [QualifierName] => Array ( [0] => deficiency [1] => genetics ) ) [5] => SimpleXMLElement Object ( [DescriptorName] => Child ) [6] => SimpleXMLElement Object ( [DescriptorName] => Homozygote ) [7] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [8] => SimpleXMLElement Object ( [DescriptorName] => Lung ) [9] => SimpleXMLElement Object ( [DescriptorName] => Male ) [10] => SimpleXMLElement Object ( [DescriptorName] => Mutation ) [11] => SimpleXMLElement Object ( [DescriptorName] => Neutrophil Infiltration ) [12] => SimpleXMLElement Object ( [DescriptorName] => Neutrophils [QualifierName] => immunology ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2016 [Month] => 10 [Day] => 26 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2018 [Month] => 10 [Day] => 3 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2016 [Month] => 10 [Day] => 26 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 27777981 [1] => 10.1172/jci.insight.89890 [2] => 89890 [3] => PMC5070961 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 1995 Oct;172(4):1153-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7561202 ) ) [1] => SimpleXMLElement Object ( [Citation] => Pediatr Infect Dis J. 2015 Sep;34(9):999-1002 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25933095 ) ) [2] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Jan 28;11(1):e1004625 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25629406 ) ) [3] => SimpleXMLElement Object ( [Citation] => Nature. 2006 Aug 10;442(7103):651-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16862125 ) ) [4] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2006 Dec;7(12):1258-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17110942 ) ) [5] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2009 Oct 29;361(18):1727-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19864672 ) ) [6] => SimpleXMLElement Object ( [Citation] => J Bacteriol. 1998 Jun;180(12):3031-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9620950 ) ) [7] => SimpleXMLElement Object ( [Citation] => Blood. 2014 Jul 24;124(4):590-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24948657 ) ) [8] => SimpleXMLElement Object ( [Citation] => Am J Respir Crit Care Med. 1995 Sep;152(3):1079-86 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7663787 ) ) [9] => SimpleXMLElement Object ( [Citation] => Clin Microbiol Rev. 2011 Jul;24(3):490-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21734245 ) ) [10] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2006 Jun;116(6):1642-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16710478 ) ) [11] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Jan 26;11(1):e1004589 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25621893 ) ) [12] => SimpleXMLElement Object ( [Citation] => Nat Methods. 2010 Apr;7(4):248-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20354512 ) ) [13] => SimpleXMLElement Object ( [Citation] => Am J Hum Genet. 2001 May;68(5):1077-85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11309678 ) ) [14] => SimpleXMLElement Object ( [Citation] => Curr Opin Infect Dis. 2013 Jun;26(3):270-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23449139 ) ) [15] => SimpleXMLElement Object ( [Citation] => Curr Opin Infect Dis. 2011 Aug;24(4):315-22 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21666456 ) ) [16] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2016 Apr;137(4):1178-88.e1-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26521038 ) ) [17] => SimpleXMLElement Object ( [Citation] => Curr Opin Pediatr. 2013 Dec;25(6):736-47 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24240293 ) ) [18] => SimpleXMLElement Object ( [Citation] => Blood. 2010 Jun 3;115(22):4588-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20354173 ) ) [19] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2013;9(7):e1003417 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23935480 ) ) [20] => SimpleXMLElement Object ( [Citation] => Blood. 2014 Feb 6;123(6):809-21 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24227816 ) ) [21] => SimpleXMLElement Object ( [Citation] => Lancet. 2003 Nov 29;362(9398):1828-38 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14654323 ) ) [22] => SimpleXMLElement Object ( [Citation] => Nat Genet. 2014 Mar;46(3):310-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24487276 ) ) [23] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2013 Oct 31;369(18):1704-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24131138 ) ) [24] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2014 Mar;133(3):905-8.e3 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24231284 ) ) [25] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2009 Apr 30;360(18):1870-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19403905 ) ) [26] => SimpleXMLElement Object ( [Citation] => Front Cell Infect Microbiol. 2016 Apr 05;6:39 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27092298 ) ) [27] => SimpleXMLElement Object ( [Citation] => J Allergy Clin Immunol. 2015 Jun;135(6):1558-68.e2 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25702837 ) ) [28] => SimpleXMLElement Object ( [Citation] => Sci Transl Med. 2012 Dec 19;4(165):165rv13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23253612 ) ) [29] => SimpleXMLElement Object ( [Citation] => Eukaryot Cell. 2007 Sep;6(9):1552-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17630330 ) ) [30] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Dec 17;11(12):e1005293 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26679537 ) ) [31] => SimpleXMLElement Object ( [Citation] => Mycopathologia. 2015 Jun;179(5-6):347-57 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25790941 ) ) [32] => SimpleXMLElement Object ( [Citation] => J Infect Dis. 2015 Apr 15;211(8):1241-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25057046 ) ) [33] => SimpleXMLElement Object ( [Citation] => Adv Appl Microbiol. 2003;52:245-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12964247 ) ) [34] => SimpleXMLElement Object ( [Citation] => Blood. 2013 Mar 28;121(13):2385-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23335372 ) ) [35] => SimpleXMLElement Object ( [Citation] => Cold Spring Harb Perspect Med. 2014 Jun 02;4(6):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24890837 ) ) [36] => SimpleXMLElement Object ( [Citation] => Clin Microbiol Rev. 1999 Apr;12(2):310-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10194462 ) ) [37] => SimpleXMLElement Object ( [Citation] => Cell Host Microbe. 2015 Apr 8;17(4):507-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25771792 ) ) [38] => SimpleXMLElement Object ( [Citation] => PLoS One. 2008 Jul 09;3(7):e2655 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18648542 ) ) ) ) ) ) [14] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => Publisher [Owner] => NLM ) [PMID] => 27588307 [DateRevised] => SimpleXMLElement Object ( [Year] => 2019 [Month] => 11 [Day] => 20 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2379-3708 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Print ) [Volume] => 1 [Issue] => 13 [PubDate] => SimpleXMLElement Object ( [Year] => 2016 [Month] => Aug [Day] => 18 ) ) [Title] => JCI insight [ISOAbbreviation] => JCI Insight ) [ArticleTitle] => Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. [ELocationID] => e88782 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common mutation was c.967_979del13. All but one patient had anti-IFN-ω autoantibodies, including 4 of 5 patients without biallelic mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjögren's-like syndrome, uncommon entities in European APECED cohorts, affected 40%-80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4 T cells and CD21CD38 B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and potentially prevent life-threatening endocrine complications. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ferre [ForeName] => Elise M N [Initials] => EM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rose [ForeName] => Stacey R [Initials] => SR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rosenzweig [ForeName] => Sergio D [Initials] => SD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Burbelo [ForeName] => Peter D [Initials] => PD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Romito [ForeName] => Kimberly R [Initials] => KR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Niemela [ForeName] => Julie E [Initials] => JE [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rosen [ForeName] => Lindsey B [Initials] => LB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Break [ForeName] => Timothy J [Initials] => TJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Gu [ForeName] => Wenjuan [Initials] => W [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., National Cancer Institute (NCI) Campus at Frederick, Frederick, Maryland, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hunsberger [ForeName] => Sally [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biostatistics Research Branch, Division of Clinical Research, NIAID, NIH, Bethesda, Maryland, USA. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Browne [ForeName] => Sarah K [Initials] => SK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hsu [ForeName] => Amy P [Initials] => AP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rampertaap [ForeName] => Shakuntala [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Collar [ForeName] => Amanda L [Initials] => AL [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kong [ForeName] => Heidi H [Initials] => HH [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Dermatology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lee [ForeName] => Chyi-Chia Richard [Initials] => CR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Chascsa [ForeName] => David [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Translational Hepatology Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Simcox [ForeName] => Thomas [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Translational Hepatology Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pham [ForeName] => Angela [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bondici [ForeName] => Anamaria [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Natarajan [ForeName] => Mukil [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Monsale [ForeName] => Joseph [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kleiner [ForeName] => David E [Initials] => DE [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Dermatology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Quezado [ForeName] => Martha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Dermatology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Alevizos [ForeName] => Ilias [Initials] => I [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Sjögren's Syndrome and Salivary Gland Dysfunction Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA. ) ) [26] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Moutsopoulos [ForeName] => Niki M [Initials] => NM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA. ) ) [27] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yockey [ForeName] => Lynne [Initials] => L [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA; Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [28] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Frein [ForeName] => Cathleen [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., National Cancer Institute (NCI) Campus at Frederick, Frederick, Maryland, USA. ) ) [29] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Soldatos [ForeName] => Ariane [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Undiagnosed Diseases Program, Common Fund, NIH Office of the Director and National Human Genome Research Institute, Bethesda, Maryland, USA. ) ) [30] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Calvo [ForeName] => Katherine R [Initials] => KR [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Hematology Section, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [31] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Adjemian [ForeName] => Jennifer [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Epidemiology Unit, Laboratory of Clinical Infectious Diseases, NIH, Bethesda, Maryland, USA. ) ) [32] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Similuk [ForeName] => Morgan N [Initials] => MN [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Immunology, NIAID, NIH, Bethesda, Maryland, USA. ) ) [33] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lang [ForeName] => David M [Initials] => DM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Pediatric Consult Service, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [34] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Stone [ForeName] => Kelly D [Initials] => KD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [35] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Uzel [ForeName] => Gulbu [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [36] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kopp [ForeName] => Jeffrey B [Initials] => JB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA. ) ) [37] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bishop [ForeName] => Rachel J [Initials] => RJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Consult Services Section, National Eye Institute, NIH, Bethesda, Maryland, USA. ) ) [38] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA. ) ) [39] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Olivier [ForeName] => Kenneth N [Initials] => KN [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA. ) ) [40] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fleisher [ForeName] => Thomas A [Initials] => TA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA. ) ) [41] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Heller [ForeName] => Theo [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Translational Hepatology Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA. ) ) [42] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Winer [ForeName] => Karen K [Initials] => KK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Pediatric Growth and Nutrition Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA. ) ) [43] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001C [Acronym] => RC [Agency] => CCR NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001E [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => JCI Insight [NlmUniqueID] => 101676073 [ISSNLinking] => 2379-3708 ) [CoiStatement] => The authors have declared that no conflict of interest exists. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2016 [Month] => 9 [Day] => 3 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2016 [Month] => 9 [Day] => 3 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2016 [Month] => 9 [Day] => 3 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 27588307 [1] => 10.1172/jci.insight.88782 [2] => PMC5004733 [3] => NIHMS811636 ) ) [nihms] => SimpleXMLElement Object ( ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Medicine (Baltimore). 1981 Sep;60(5):355-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7024719 ) ) [1] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 1993 Nov;92 (5):2377-85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8227354 ) ) [2] => SimpleXMLElement Object ( [Citation] => BMC Biotechnol. 2005 Aug 18;5:22 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16109166 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Pediatr Endocrinol Metab. 2002 Nov-Dec;15(9):1491-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12503856 ) ) [4] => SimpleXMLElement Object ( [Citation] => Diabetes Care. 2008 Sep;31(9):1824-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18535195 ) ) [5] => SimpleXMLElement Object ( [Citation] => Lancet. 1998 Jul 25;352(9124):279-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9690408 ) ) [6] => SimpleXMLElement Object ( [Citation] => Mayo Clin Proc. 1998 Dec;73(12):1161-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9868413 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2006 Aug;91(8):2843-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16684821 ) ) [8] => SimpleXMLElement Object ( [Citation] => Pediatr Endocrinol Rev. 2009 Dec;7(2):15-28 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20118890 ) ) [9] => SimpleXMLElement Object ( [Citation] => PLoS Med. 2006 Jul;3(7):e289 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16784312 ) ) [10] => SimpleXMLElement Object ( [Citation] => Ann Rheum Dis. 2002 Jun;61(6):554-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12006334 ) ) [11] => SimpleXMLElement Object ( [Citation] => Expert Rev Vaccines. 2010 Jun;9(6):567-78 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20518713 ) ) [12] => SimpleXMLElement Object ( [Citation] => Blood. 2011 Aug 4;118(5):1294-304 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21562046 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2012 Apr;97(4):1114-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22344197 ) ) [14] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 1990 Jun 28;322(26):1829-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2348835 ) ) [15] => SimpleXMLElement Object ( [Citation] => Hum Mutat. 1999;13(1):69-74 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9888391 ) ) [16] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2010 Feb 15;207(2):291-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20123958 ) ) [17] => SimpleXMLElement Object ( [Citation] => Genes Immun. 2008 Mar;9(2):130-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18200029 ) ) [18] => SimpleXMLElement Object ( [Citation] => Blood. 2010 Dec 2;116(23):4848-58 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20716769 ) ) [19] => SimpleXMLElement Object ( [Citation] => J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1257-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24945421 ) ) [20] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4396-401 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19251657 ) ) [21] => SimpleXMLElement Object ( [Citation] => Scand J Immunol. 2010 Jun;71(6):459-67 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20500699 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Pediatr Endocrinol Metab. 2006 Nov;19(11):1343-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17220063 ) ) [23] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2007 Feb;92(2):595-603 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17118990 ) ) [24] => SimpleXMLElement Object ( [Citation] => Clin Chem. 1997 Aug;43(8 Pt 1):1392-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9267319 ) ) [25] => SimpleXMLElement Object ( [Citation] => PLoS One. 2012;7(9):e45216 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23028856 ) ) [26] => SimpleXMLElement Object ( [Citation] => Lancet. 1992 Jun 27;339(8809):1559-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1351548 ) ) [27] => SimpleXMLElement Object ( [Citation] => Clin Endocrinol (Oxf). 2001 Feb;54(2):211-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11207636 ) ) [28] => SimpleXMLElement Object ( [Citation] => J Intern Med. 2009 May;265(5):514-29 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19382991 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [30] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2008 May;118(5):1712-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18414681 ) ) [31] => SimpleXMLElement Object ( [Citation] => Clin Genet. 2006 Oct;70(4):348-54 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16965330 ) ) [32] => SimpleXMLElement Object ( [Citation] => Annu Rev Immunol. 2009;27:287-312 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19302042 ) ) [33] => SimpleXMLElement Object ( [Citation] => Blood. 2011 Aug 4;118(5):1305-15 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21543762 ) ) [34] => SimpleXMLElement Object ( [Citation] => Am J Hum Genet. 1998 Dec;63(6):1675-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9837820 ) ) [35] => SimpleXMLElement Object ( [Citation] => Horm Res Paediatr. 2010;73(6):449-57 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20407228 ) ) [36] => SimpleXMLElement Object ( [Citation] => J Pediatr Endocrinol Metab. 2005 Feb;18(2):155-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15751604 ) ) [37] => SimpleXMLElement Object ( [Citation] => Immunobiology. 2002 Dec;206(5):502-13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12607725 ) ) [38] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2016 Aug;101(8):2975-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27253668 ) ) [39] => SimpleXMLElement Object ( [Citation] => Blood. 2010 Jun 17;115(24):5026-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20231422 ) ) [40] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2005 Aug;90(8):4930-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15886230 ) ) [41] => SimpleXMLElement Object ( [Citation] => J Transl Med. 2010 Oct 14;8:97 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20946647 ) ) [42] => SimpleXMLElement Object ( [Citation] => Science. 2002 Nov 15;298(5597):1395-401 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12376594 ) ) [43] => SimpleXMLElement Object ( [Citation] => Pediatr Pulmonol. 2012 Jan;47(1):84-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21901851 ) ) [44] => SimpleXMLElement Object ( [Citation] => Clin Immunol. 2004 Nov;113(2):161-71 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15451473 ) ) [45] => SimpleXMLElement Object ( [Citation] => Science. 2014 Sep 26;345(6204):1623-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25213377 ) ) [46] => SimpleXMLElement Object ( [Citation] => Eur J Endocrinol. 2008 May;158(5):705-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18426830 ) ) [47] => SimpleXMLElement Object ( [Citation] => Horm Res Paediatr. 2014;82(2):127-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25059117 ) ) [48] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 1997 May;82(5):1440-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9141530 ) ) [49] => SimpleXMLElement Object ( [Citation] => J Immunol. 2015 Jul 1;195(1):71-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26034175 ) ) [50] => SimpleXMLElement Object ( [Citation] => Immunity. 2015 Jun 16;42(6):1185-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26084028 ) ) [51] => SimpleXMLElement Object ( [Citation] => J Clin Immunol. 2012 Apr;32(2):238-45 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22170314 ) ) [52] => SimpleXMLElement Object ( [Citation] => Blood. 2008 Jan 1;111(1):77-85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17898316 ) ) [53] => SimpleXMLElement Object ( [Citation] => J Vis Exp. 2009 Oct 07;(32):null [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19812534 ) ) [54] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2010 Feb 15;207(2):299-308 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20123959 ) ) [55] => SimpleXMLElement Object ( [Citation] => J Clin Immunol. 2015 Jul;35(5):463-78 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26141571 ) ) [56] => SimpleXMLElement Object ( [Citation] => Sci Transl Med. 2013 Oct 9;5(206):206ra139 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24107778 ) ) [57] => SimpleXMLElement Object ( [Citation] => PLoS One. 2012;7(2):e32001 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22363785 ) ) [58] => SimpleXMLElement Object ( [Citation] => Am J Med. 1991 Dec;91(6):625-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1750432 ) ) [59] => SimpleXMLElement Object ( [Citation] => J Med Genet. 1992 Nov;29(11):824-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1453436 ) ) [60] => SimpleXMLElement Object ( [Citation] => J Clin Endocrinol Metab. 2001 Oct;86(10):4747-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11600535 ) ) [61] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2009 Mar 1;48(5):503-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19191635 ) ) ) ) ) ) [15] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 27191829 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2017 [Month] => 07 [Day] => 26 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2018 [Month] => 11 [Day] => 13 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2150-5608 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 7 [Issue] => 7 [PubDate] => SimpleXMLElement Object ( [Year] => 2016 [Month] => 10 [Day] => 02 ) ) [Title] => Virulence [ISOAbbreviation] => Virulence ) [ArticleTitle] => Batf3-dependent CD103(+) dendritic cell accumulation is dispensable for mucosal and systemic antifungal host defense. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 826-35 ) [ELocationID] => 10.1080/21505594.2016.1186324 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Dendritic cells (DCs) are critical for defense against a variety of pathogens and the formation of adaptive immune responses. The transcription factor Batf3 is critical for the development of CD103(+)CD11b(-) DCs, which promote IL-12-dependent protective immunity during viral and parasitic infections, dampen Th2 immunity during helminthic infection, and exert detrimental effects during bacterial infection. Whether CD103(+) DCs modulate immunity during systemic or mucosal fungal disease remains unknown. Herein, we report that Batf3 is critical for accumulation of CD103(+) DCs in the kidney and tongue at steady state, for their expansion during systemic and oropharyngeal candidiasis, and for tissue-specific production of IL-12 in kidney but not tongue during systemic and oropharyngeal candidiasis, respectively. Importantly, deficiency of CD103(+) DCs does not impair survival or fungal clearance during systemic or oropharyngeal candidiasis, indicating that Batf3-dependent CD103(+) DC accumulation mediates pathogen- and tissue-specific immune effects. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Break [ForeName] => Timothy J [Initials] => TJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => a Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hoffman [ForeName] => Kevin W [Initials] => KW [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => b Department of Microbiology , Icahn School of Medicine at Mount Sinai , New York , NY , USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => a Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lee [ForeName] => Chyi-Chia Richard [Initials] => CC [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => c Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda , MD , USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lim [ForeName] => Jean K [Initials] => JK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => b Department of Microbiology , Icahn School of Medicine at Mount Sinai , New York , NY , USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => a Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => T32 AI007647 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => R01 AI108715 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Extramural [2] => Research Support, N.I.H., Intramural ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2016 [Month] => 05 [Day] => 18 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Virulence [NlmUniqueID] => 101531386 [ISSNLinking] => 2150-5594 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Antigens, CD ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Basic-Leucine Zipper Transcription Factors ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Integrin alpha Chains ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Repressor Proteins ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => SNFT protein, mouse ) [5] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => alpha E integrins ) [6] => SimpleXMLElement Object ( [RegistryNumber] => 187348-17-0 [NameOfSubstance] => Interleukin-12 ) ) ) [CitationSubset] => IM [CommentsCorrectionsList] => SimpleXMLElement Object ( [CommentsCorrections] => SimpleXMLElement Object ( [@attributes] => Array ( [RefType] => CommentIn ) [RefSource] => Virulence. 2016 Oct 2;7(7):745-7 [PMID] => 27336198 ) ) [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Antigens, CD [QualifierName] => analysis ) [2] => SimpleXMLElement Object ( [DescriptorName] => Basic-Leucine Zipper Transcription Factors [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [3] => SimpleXMLElement Object ( [DescriptorName] => Candidiasis, Invasive [QualifierName] => Array ( [0] => immunology [1] => microbiology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Candidiasis, Oral [QualifierName] => Array ( [0] => immunology [1] => microbiology ) ) [5] => SimpleXMLElement Object ( [DescriptorName] => Cell Proliferation ) [6] => SimpleXMLElement Object ( [DescriptorName] => Dendritic Cells [QualifierName] => Array ( [0] => immunology [1] => physiology ) ) [7] => SimpleXMLElement Object ( [DescriptorName] => Immunity, Innate ) [8] => SimpleXMLElement Object ( [DescriptorName] => Integrin alpha Chains [QualifierName] => Array ( [0] => analysis [1] => deficiency ) ) [9] => SimpleXMLElement Object ( [DescriptorName] => Interleukin-12 [QualifierName] => Array ( [0] => biosynthesis [1] => immunology ) ) [10] => SimpleXMLElement Object ( [DescriptorName] => Kidney [QualifierName] => immunology ) [11] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [12] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred C57BL ) [13] => SimpleXMLElement Object ( [DescriptorName] => Repressor Proteins [QualifierName] => Array ( [0] => genetics [1] => immunology ) ) [14] => SimpleXMLElement Object ( [DescriptorName] => Tongue [QualifierName] => immunology ) ) ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Batf3 [1] => CD103 [2] => IL-12 [3] => dendritic cells [4] => fungal infection [5] => innate immunity [6] => oropharyngeal candidiasis [7] => systemic candidiasis ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2016 [Month] => 5 [Day] => 19 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2016 [Month] => 5 [Day] => 19 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2017 [Month] => 7 [Day] => 27 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 27191829 [1] => PMC5029292 [2] => 10.1080/21505594.2016.1186324 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Med Mycol. 2014 Aug;52(6):555-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25023483 ) ) [1] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2014 Jul 17;10 (7):e1004276 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25033445 ) ) [2] => SimpleXMLElement Object ( [Citation] => Nat Protoc. 2012 Mar 08;7(4):637-42 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22402633 ) ) [3] => SimpleXMLElement Object ( [Citation] => Microbes Infect. 2007 Apr;9(5):615-22 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17383212 ) ) [4] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2014 Mar 27;370(13):1198-208 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24670166 ) ) [5] => SimpleXMLElement Object ( [Citation] => Blood. 2013 Feb 28;121(9):1574-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23297132 ) ) [6] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2013 Dec;123(12):5035-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24177428 ) ) [7] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2001 Nov;69(11):6813-22 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11598054 ) ) [8] => SimpleXMLElement Object ( [Citation] => Arthritis Res Ther. 2012 Jul 23;14(4):217 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22838497 ) ) [9] => SimpleXMLElement Object ( [Citation] => Immunity. 2011 Aug 26;35(2):236-48 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21867927 ) ) [10] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2003 Dec;33(12):3409-17 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14635050 ) ) [11] => SimpleXMLElement Object ( [Citation] => Science. 2008 Nov 14;322(5904):1097-100 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19008445 ) ) [12] => SimpleXMLElement Object ( [Citation] => Blood. 2015 Feb 26;125(9):1452-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25597637 ) ) [13] => SimpleXMLElement Object ( [Citation] => Clin Infect Dis. 2008 Jan 1;46(1):120-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18171227 ) ) [14] => SimpleXMLElement Object ( [Citation] => Immunity. 2014 May 15;40(5):642-56 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24837101 ) ) [15] => SimpleXMLElement Object ( [Citation] => Nature. 2012 Oct 25;490(7421):502-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22992524 ) ) [16] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2015 Dec;83(12):4719-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26416905 ) ) [17] => SimpleXMLElement Object ( [Citation] => Clin Microbiol Rev. 2004 Oct;17(4):729-59, table of contents [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15489345 ) ) [18] => SimpleXMLElement Object ( [Citation] => Immunity. 2011 Aug 26;35(2):249-59 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21867928 ) ) [19] => SimpleXMLElement Object ( [Citation] => J Innate Immun. 2011;3(2):180-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21063074 ) ) [20] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2016 Jan 11;213(1):35-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26712805 ) ) [21] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2014 Jan;15(1):98-108 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24292363 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2009 Feb 16;206(2):299-311 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19204111 ) ) [23] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 1997 Dec 25;337(26):1896-903 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9407158 ) ) [24] => SimpleXMLElement Object ( [Citation] => Immunity. 2015 Feb 17;42(2):356-66 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25680275 ) ) [25] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2015 Oct;15(10):630-42 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26388329 ) ) [26] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2013;9(4):e1003315 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23637604 ) ) [27] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2013;9(12):e1003801 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24367259 ) ) [28] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2011 Jul 14;365(2):127-38 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21524210 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2010 Apr 12;207(4):823-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20351058 ) ) [30] => SimpleXMLElement Object ( [Citation] => PLoS Pathog. 2015 Oct 02;11(10):e1005164 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26431538 ) ) [31] => SimpleXMLElement Object ( [Citation] => Infect Immun. 2015 Mar;83(3):958-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25547797 ) ) [32] => SimpleXMLElement Object ( [Citation] => J Leukoc Biol. 2004 Jan;75(1):117-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14525965 ) ) ) ) ) ) [16] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 27044504 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2016 [Month] => 10 [Day] => 06 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2018 [Month] => 11 [Day] => 13 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2049-2618 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 4 [PubDate] => SimpleXMLElement Object ( [Year] => 2016 [Month] => Apr [Day] => 05 ) ) [Title] => Microbiome [ISOAbbreviation] => Microbiome ) [ArticleTitle] => Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 13 ) [ELocationID] => 10.1186/s40168-016-0159-0 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Array ( [0] => Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. [1] => Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. [2] => Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis. ) ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Falcone [ForeName] => E Liana [Initials] => EL [Identifier] => http://orcid.org/0000-0002-5486-1549 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. emilia.falcone@nih.gov. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Abusleme [ForeName] => Loreto [Initials] => L [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Swamydas [ForeName] => Muthulekha [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lionakis [ForeName] => Michail S [Initials] => MS [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ding [ForeName] => Li [Initials] => L [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hsu [ForeName] => Amy P [Initials] => AP [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Zelazny [ForeName] => Adrian M [Initials] => AM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Microbiology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Moutsopoulos [ForeName] => Niki M [Initials] => NM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Oral Immunity and Inflammation Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kuhns [ForeName] => Douglas B [Initials] => DB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Neutrophil Monitoring Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Deming [ForeName] => Clay [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Quiñones [ForeName] => Mariam [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Segre [ForeName] => Julia A [Initials] => JA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bryant [ForeName] => Clare E [Initials] => CE [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, UK. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Holland [ForeName] => Steven M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001C [Acronym] => RC [Agency] => CCR NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001E [Acronym] => CA [Agency] => NCI NIH HHS [Country] => United States ) [2] => SimpleXMLElement Object ( [GrantID] => HHSN261200800001E [Agency] => PHS HHS [Country] => United States ) [3] => SimpleXMLElement Object ( [Agency] => Intramural NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Extramural [2] => Research Support, N.I.H., Intramural ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2016 [Month] => 04 [Day] => 05 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => Microbiome [NlmUniqueID] => 101615147 [ISSNLinking] => 2049-2618 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Reactive Oxygen Species ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 53-59-8 [NameOfSubstance] => NADP ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 9042-14-2 [NameOfSubstance] => Dextran Sulfate ) [3] => SimpleXMLElement Object ( [RegistryNumber] => EC 1.6.3.- [NameOfSubstance] => NADPH Oxidases ) [4] => SimpleXMLElement Object ( [RegistryNumber] => EC 1.6.3.1 [NameOfSubstance] => neutrophil cytosolic factor 1 ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Adult ) [1] => SimpleXMLElement Object ( [DescriptorName] => Animals )