4,156 results match your criteria Lymphocytic Choriomeningitis


Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation.

Blood 2020 Jun 26. Epub 2020 Jun 26.

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, Pennsylvania, United States.

Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threatening hyperinflammatory syndromes typically associated with underlying hematologic and rheumatic diseases, respectively. Familial HLH is associated with genetic cytotoxic impairment, and thereby to excessive antigen presentation. Extreme elevation of serum Interleukin (IL)-18 has been observed specifically in patients with MAS, making it a promising therapeutic target, but how IL-18 promotes hyperinflammation remains unknown. Read More

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http://dx.doi.org/10.1182/blood.2019003846DOI Listing

Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition.

mBio 2020 06 23;11(3). Epub 2020 Jun 23.

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA

It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 "don't eat me" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. Read More

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http://dx.doi.org/10.1128/mBio.01293-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315125PMC

IgM Antibody Repertoire Fingerprints in Mice Are Personalized but Robust to Viral Infection Status.

Front Cell Infect Microbiol 2020 28;10:254. Epub 2020 May 28.

Department of Biosystems and Engineering, ETH Zurich, Basel, Switzerland.

Antibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-resident B cells in the setting of viral infection remains largely uncharacterized. Read More

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http://dx.doi.org/10.3389/fcimb.2020.00254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270205PMC

Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection.

Front Immunol 2020 29;11:986. Epub 2020 May 29.

Institute of Microbiology, ETH Zurich, Zurich, Switzerland.

CD8 T cells play a crucial role in providing protection from viral infections. It has recently been established that a subset of CD8 T cells expressing Tcf1 are responsible for sustaining exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection. Many of these studies, however, have been performed using T cell receptor (TCR) transgenic mice, in which CD8 T cells express a monoclonal TCR specific for the LCMV glycoprotein. Read More

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http://dx.doi.org/10.3389/fimmu.2020.00986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272574PMC

-3 Polyunsaturated Fatty Acids Impede the TCR Mobility and the TCR-pMHC Interaction of Anti-Viral CD8+ T Cells.

Viruses 2020 Jun 12;12(6). Epub 2020 Jun 12.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

The immune-suppressive effects of omega-3 (3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whether -3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. Read More

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http://dx.doi.org/10.3390/v12060639DOI Listing

Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry.

Acta Pharm Sin B 2020 May 5;10(5):789-798. Epub 2020 Mar 5.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics. Dietary supplements, especially natural products that are edible and safe for human use, are a good source of drug discovery with potential for uncovering novel applications. In this study, we tested 40 natural products of dietary supplements and identified capsaicin, a common dietary supplement abundant in chili peppers, as an inhibitor of Lassa virus (LASV) entry with EC of 6. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276894PMC

Lentiviral-Vector-Based Dendritic Cell Vaccine Synergizes with Checkpoint Blockade to Clear Chronic Viral Infection.

Mol Ther 2020 May 20. Epub 2020 May 20.

Department of Microbiology, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address:

Dendritic cell vaccines are a promising strategy for the treatment of cancer and infectious diseases but have met with mixed success. We report on a lentiviral vector-based dendritic cell vaccine strategy that generates a cluster of differentiation 8 (CD8) T cell response that is much stronger than that achieved by standard peptide-pulsing approaches. The strategy was tested in the mouse lymphocytic choriomeningitis virus (LCMV) model. Read More

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http://dx.doi.org/10.1016/j.ymthe.2020.05.018DOI Listing

Preceding Viral Infections Do Not Imprint Long-Term Changes in Regulatory T Cell Function.

Sci Rep 2020 May 20;10(1):8350. Epub 2020 May 20.

University of Zurich, Institute of Experimental Immunology, Zurich, 8057, Switzerland.

Regulatory T cells (T) maintain peripheral self-tolerance and limit immune mediated pathology. Like effector T cells, T can specialize in T1-dominated immune responses and co-express T-bet together with Foxp3. This allows for expression of CXCR3 and efficient homing to sites of T1 responses. Read More

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http://dx.doi.org/10.1038/s41598-020-65212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239864PMC

Trigger-dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis.

Eur J Immunol 2020 May 17. Epub 2020 May 17.

Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Institute for Immunodeficiency, Medical Center, University of Freiburg, Germany.

Familial hemophagocytic lymphohistiocytosis (FHL) is a hyperinflammatory syndrome affecting patients with genetic cytotoxicity defects. Perforin-deficient (PKO) mice recapitulate the full clinical picture of FHL after infection with lymphocytic choriomeningitis virus (LCMV). Hyperactivated CD8 T cells and IFN-γ have been identified as the key drivers of FHL and represent targets for therapeutic interventions. Read More

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http://dx.doi.org/10.1002/eji.201948123DOI Listing

CD49aCD49b NK cells induced by viral infection reflect an activated state of conventional NK cells.

Sci China Life Sci 2020 Apr 23. Epub 2020 Apr 23.

Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.

Natural killer (NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic and functional heterogeneity of NK cells. Here, using murine models of acute and chronic lymphocytic choriomeningitis virus infection, we observed that a CD49a CD49b NK cell subset emerged in the liver and other tissues, and underwent vigorous expansion following viral infection, before progressively decreasing in cell number. Read More

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http://dx.doi.org/10.1007/s11427-019-1665-1DOI Listing

Cyclophilin D Regulates Antiviral CD8 T Cell Survival in a Cell-Extrinsic Manner.

Immunohorizons 2020 Apr 24;4(4):217-230. Epub 2020 Apr 24.

Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3G 1Y6, Canada;

CD8 T cell-mediated immunity is critical for host defense against viruses and requires mitochondria-mediated type I IFN (IFN-I) signaling for optimal protection. Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8 T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8 T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. Read More

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http://dx.doi.org/10.4049/immunohorizons.2000016DOI Listing

A Randomized Dose-Escalating Phase I Trial of a Replication-Deficient Lymphocytic Choriomeningitis Virus Vector-Based Vaccine Against Human Cytomegalovirus.

J Infect Dis 2020 Apr 21. Epub 2020 Apr 21.

Hookipa Pharma Inc., New York, New York, USA.

Background: A vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection.

Methods: HB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3. Read More

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http://dx.doi.org/10.1093/infdis/jiaa121DOI Listing

Contribution of STAT1 to innate and adaptive immunity during type I interferon-mediated lethal virus infection.

PLoS Pathog 2020 04 20;16(4):e1008525. Epub 2020 Apr 20.

School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia.

Signal transducers and activators of transcription (STAT) 1 is critical for cellular responses to type I interferons (IFN-Is), with the capacity to determine the outcome of viral infection. We previously showed that while wildtype (WT) mice develop mild disease and survive infection with lymphocytic choriomeningitis virus (LCMV), LCMV infection of STAT1-deficient mice results in a lethal wasting disease that is dependent on IFN-I and CD4+ cells. IFN-Is are considered to act as a bridge between innate and adaptive immunity. Read More

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http://dx.doi.org/10.1371/journal.ppat.1008525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192509PMC

Immunotherapeutic Blockade of CD47 Inhibitory Signaling Enhances Innate and Adaptive Immune Responses to Viral Infection.

Cell Rep 2020 Apr;31(2):107494

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA. Electronic address:

Paradoxically, early host responses to infection include the upregulation of the antiphagocytic molecule, CD47. This suggests that CD47 blockade could enhance antigen presentation and subsequent immune responses. Indeed, mice treated with anti-CD47 monoclonal antibody following lymphocytic choriomeningitis virus infections show increased activation of both macrophages and dendritic cells (DCs), enhancement of the kinetics and potency of CD8 T cell responses, and significantly improved virus control. Read More

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http://dx.doi.org/10.1016/j.celrep.2020.03.058DOI Listing
April 2020
7.207 Impact Factor

Retinoic Acid Modulates Hyperactive T Cell Responses and Protects Vitamin A-Deficient Mice against Persistent Lymphocytic Choriomeningitis Virus Infection.

J Immunol 2020 Jun 13;204(11):2984-2994. Epub 2020 Apr 13.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;

Vitamin A deficiency (VAD) is a major public health problem and is associated with increased host susceptibility to infection; however, how VAD influences viral infection remains unclear. Using a persistent lymphocytic choriomeningitis virus infection model, we showed in this study that although VAD did not alter innate type I IFN production, infected VAD mice had hyperactive, virus-specific T cell responses at both the acute and contraction stages, showing significantly decreased PD-1 but increased cytokine (IFN-γ, TNF-α, and IL-2) expression by T cells. Compared with control mice, VAD mice displayed excessive inflammation and more severe liver pathology, with increased death during persistent infection. Read More

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http://dx.doi.org/10.4049/jimmunol.1901091DOI Listing
June 2020
4.922 Impact Factor

Emerging and neglected zoonoses in transplant population.

World J Transplant 2020 Mar;10(3):47-63

Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Croatia.

Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Read More

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http://dx.doi.org/10.5500/wjt.v10.i3.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109593PMC

Granulocyte/Macrophage Colony-Stimulating Factor-Derived Macrophages Exhibit Distinctive Early Immune Response to Lymphocytic Choriomeningitis Virus Infection.

Viral Immunol 2020 Apr 7. Epub 2020 Apr 7.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) modulate differentiation and immune functions of macrophages (MΦ). Our aim was to evaluate how different MΦ differentiation conditions influence the MΦ response to virus infection. To address this, we differentiated bone marrow-derived MΦ in either GM-CSF or M-CSF and measured the cytokine responses to two different strains of lymphocytic choriomeningitis virus (LCMV) (clone 13; Cl13 or Armstrong; ARM). Read More

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http://dx.doi.org/10.1089/vim.2019.0178DOI Listing

TNIK signaling imprints CD8 T cell memory formation early after priming.

Nat Commun 2020 Apr 2;11(1):1632. Epub 2020 Apr 2.

Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, 3010, Switzerland.

Co-stimulatory signals, cytokines and transcription factors regulate the balance between effector and memory cell differentiation during T cell activation. Here, we analyse the role of the TRAF2-/NCK-interacting kinase (TNIK), a signaling molecule downstream of the tumor necrosis factor superfamily receptors such as CD27, in the regulation of CD8 T cell fate during acute infection with lymphocytic choriomeningitis virus. Priming of CD8 T cells induces a TNIK-dependent nuclear translocation of β-catenin with consecutive Wnt pathway activation. Read More

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http://dx.doi.org/10.1038/s41467-020-15413-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118140PMC

Chronic viral infections impinge on naive bystander CD8 T cells.

Immun Inflamm Dis 2020 Mar 26. Epub 2020 Mar 26.

Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland.

Introduction: Epidemiological data suggest that persistent viral infections impair immune homeostasis and immune responsiveness. Previous studies showed that chronic virus infections negatively impact bystander T-cell differentiation and memory formation but there is limited knowledge of how chronic virus infections impinge on heterologous naive T-cell populations.

Methods: We used adoptive transfer of naive CD8 T cells with defined nonviral specificity into hosts, which were subsequently chronically infected with lymphocytic choriomeningitis virus, followed by analyses of numeric, phenotypic, and functional changes provoked in the chronically infected host. Read More

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http://dx.doi.org/10.1002/iid3.300DOI Listing

Structural insight into arenavirus replication machinery.

Nature 2020 03 18;579(7800):615-619. Epub 2020 Mar 18.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health. These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome. Viral polymerases are one of the leading antiviral therapeutic targets. Read More

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http://dx.doi.org/10.1038/s41586-020-2114-2DOI Listing

Protein Kinase C-η Deficiency Does Not Impair Antiviral Immunity and CD8 T Cell Activation.

J Immunol 2020 May 20;204(9):2439-2446. Epub 2020 Mar 20.

Division of Cell Biology, La Jolla Institute for Immunology, La Jolla, CA 92037

We reported that protein kinase C-η (PKCη) forms a novel (to our knowledge) signaling complex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs). This complex is required for the contact-dependent suppressive activity of Tregs, including suppression of antitumor immunity. However, the importance of PKCη in protective immunity mediated by T effector cells remains unclear. Read More

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http://dx.doi.org/10.4049/jimmunol.1900963DOI Listing

Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis.

J Virol 2020 May 18;94(11). Epub 2020 May 18.

Institute of Cellular Virology, ZMBE, University of Münster, Münster, Germany

Human papillomavirus 16 (HPV16), the leading cause of cervical cancer, exploits a novel endocytic pathway during host cell entry. This mechanism shares many requirements with macropinocytosis but differs in the mode of vesicle formation. Previous work indicated a role of the epidermal growth factor receptor (EGFR) in HPV16 endocytosis. Read More

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http://dx.doi.org/10.1128/JVI.02143-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269448PMC

Mouse Models of Virus-Induced Type 1 Diabetes.

Methods Mol Biol 2020 ;2128:93-105

The Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.

Virus infections have been linked to the induction of autoimmunity and disease development in human type 1 diabetes. Experimental models have been instrumental in deciphering processes leading to break of immunological tolerance and type 1 diabetes development. Animal models have also been useful for proof-of-concept studies and for preclinical testing of new therapeutic interventions. Read More

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http://dx.doi.org/10.1007/978-1-0716-0385-7_7DOI Listing
January 2020

Leukemia Inhibitory Factor Inhibits Plasmacytoid Dendritic Cell Function and Development.

J Immunol 2020 Apr 13;204(8):2257-2268. Epub 2020 Mar 13.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and

Plasmacytoid dendritic cells (pDCs) produce abundant type I IFNs (IFN-I) in response to viral nucleic acids. Generation of pDCs from bone marrow dendritic cell (DC) progenitors and their maintenance is driven by the transcription factor E2-2 and inhibited by its repressor Id2. In this study, we find that mouse pDCs selectively express the receptor for LIF that signals through STAT3. Read More

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http://dx.doi.org/10.4049/jimmunol.1900604DOI Listing

Landornamides: Antiviral Ornithine-Containing Ribosomal Peptides Discovered through Genome Mining.

Angew Chem Int Ed Engl 2020 Jul 18;59(29):11763-11768. Epub 2020 May 18.

Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.

Proteusins are a family of bacterial ribosomal peptides that largely remain hypothetical genome-predicted metabolites. The only known members are the polytheonamide-type cytotoxins, which have complex structures due to numerous unusual posttranslational modifications (PTMs). Cyanobacteria contain large numbers of putative proteusin loci. Read More

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http://dx.doi.org/10.1002/anie.201916321DOI Listing

Re-defining T-Cell Exhaustion: Subset, Function, and Regulation.

Immune Netw 2020 Feb 20;20(1):e2. Epub 2020 Feb 20.

Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul 03722, Korea.

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. Read More

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http://dx.doi.org/10.4110/in.2020.20.e2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049579PMC
February 2020

The Variable Genomic NK Cell Receptor Locus Is a Key Determinant of CD4+ T Cell Responses During Viral Infection.

Front Immunol 2020 20;11:197. Epub 2020 Feb 20.

Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

Increasing evidence points to a key role for NK cells in controlling adaptive immune responses. In studies examining the role of CD1d on CD4+ T cell responses, we found that a line of CD1d-deficient mice on the C57BL/6J background had a homozygous 129 locus on chromosome 6 containing the entire NK cell gene cluster. Mice possessing this locus (C57BL/6. Read More

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http://dx.doi.org/10.3389/fimmu.2020.00197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044186PMC
February 2020

TIGIT limits immune pathology during viral infections.

Nat Commun 2020 03 9;11(1):1288. Epub 2020 Mar 9.

Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Co-inhibitory pathways have a fundamental function in regulating T cell responses and control the balance between promoting efficient effector functions and restricting immune pathology. The TIGIT pathway has been implicated in promoting T cell dysfunction in chronic viral infection. Importantly, TIGIT signaling is functionally linked to IL-10 expression, which has an effect on both virus control and maintenance of tissue homeostasis. Read More

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http://dx.doi.org/10.1038/s41467-020-15025-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062903PMC

Functions of acetylcholine-producing lymphocytes in immunobiology.

Curr Opin Neurobiol 2020 Jun 29;62:115-121. Epub 2020 Feb 29.

Laboratory of Immunobiology, Center for Bioelectronic Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Recent advances in neuroscience and immunology have shown that cholinergic signals are vital in the regulation of inflammation and immunity. Choline acetyltransferase (ChAT) lymphocytes have the capacity to biosynthesize and release acetylcholine, the cognate ligand for cholinergic receptors. Acetylcholine-producing T cells relay neural signals in the 'inflammatory reflex' that regulate cytokine release in spleen. Read More

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http://dx.doi.org/10.1016/j.conb.2020.01.017DOI Listing

DNA hypermethylation during tuberculosis dampens host immune responsiveness.

J Clin Invest 2020 Jun;130(6):3113-3123

Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

Mycobacterium tuberculosis (M. tuberculosis) has coevolved with humans for millennia and developed multiple mechanisms to evade host immunity. Restoring host immunity in order to improve outcomes and potentially shorten existing therapy will require identification of the full complement by which host immunity is inhibited. Read More

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http://dx.doi.org/10.1172/JCI134622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260034PMC

NK Cells Regulate CD8 T Cell Mediated Autoimmunity.

Front Cell Infect Microbiol 2020 13;10:36. Epub 2020 Feb 13.

Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada.

Elucidating key factors that regulate immune-mediated pathology is critical for developing improved strategies to treat autoimmune disease and cancer. NK cells can exhibit regulatory functions against CD8 T cells following viral infection. Here we show that while low doses of lymphocytic choriomeningitis virus (LCMV-WE) can readily induce strong CD8 T cell responses and diabetes in mice expressing the LCMV glycoprotein on β-islet cells (RIP-GP mice), hyperglycemia does not occur after infection with higher doses of LCMV. Read More

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http://dx.doi.org/10.3389/fcimb.2020.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031256PMC
February 2020

Chikungunya Virus Evades Antiviral CD8 T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues.

J Virol 2020 Apr 16;94(9). Epub 2020 Apr 16.

Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes explosive epidemics of a febrile illness characterized by debilitating arthralgia and arthritis that can endure for months to years following infection. In mouse models, CHIKV persists in joint tissues for weeks to months and is associated with chronic synovitis. Using a recombinant CHIKV strain encoding a CD8 T cell receptor epitope from ovalbumin, as well as a viral peptide-specific major histocompatibility complex class I tetramer, we interrogated CD8 T cell responses during CHIKV infection. Read More

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http://dx.doi.org/10.1128/JVI.02036-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163133PMC

Chronic virus infection drives CD8 T cell-mediated thymic destruction and impaired negative selection.

Proc Natl Acad Sci U S A 2020 03 24;117(10):5420-5429. Epub 2020 Feb 24.

Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada;

Chronic infection provokes alterations in inflammatory and suppressive pathways that potentially affect the function and integrity of multiple tissues, impacting both ongoing immune control and restorative immune therapies. Here we demonstrate that chronic lymphocytic choriomeningitis virus infection rapidly triggers severe thymic depletion, mediated by CD8 T cell-intrinsic type I interferon (IFN) and signal transducer and activator of transcription 2 (Stat2) signaling. Occurring temporal to T cell exhaustion, thymic cellularity reconstituted despite ongoing viral replication, with a rapid secondary thymic depletion following immune restoration by anti-programmed death-ligand 1 (PDL1) blockade. Read More

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http://dx.doi.org/10.1073/pnas.1913776117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071912PMC

Spatiotemporal regulation of type I interferon expression determines the antiviral polarization of CD4 T cells.

Nat Immunol 2020 03 17;21(3):321-330. Epub 2020 Feb 17.

Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Differentiation of CD4 T cells into either follicular helper T (T) or type 1 helper T (T1) cells influences the balance between humoral and cellular adaptive immunity, but the mechanisms whereby pathogens elicit distinct effector cells are incompletely understood. Here we analyzed the spatiotemporal dynamics of CD4 T cells during infection with recombinant vesicular stomatitis virus (VSV), which induces early, potent neutralizing antibodies, or recombinant lymphocytic choriomeningitis virus (LCMV), which induces a vigorous cellular response but inefficient neutralizing antibodies, expressing the same T cell epitope. Early exposure of dendritic cells to type I interferon (IFN), which occurred during infection with VSV, induced production of the cytokine IL-6 and drove T cell polarization, whereas late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into T1 cells. Read More

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http://dx.doi.org/10.1038/s41590-020-0596-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043938PMC

PD-1+ stemlike CD8 T cells are resident in lymphoid tissues during persistent LCMV infection.

Proc Natl Acad Sci U S A 2020 02 7;117(8):4292-4299. Epub 2020 Feb 7.

Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;

The migratory patterns of virus-specific CD8 T cells during chronic viral infection are not well understood. To address this issue, we have done parabiosis experiments during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. We found that despite the high frequency of virus-specific CD8 T cells in both lymphoid and nonlymphoid tissues there was minimal migration of virus-specific CD8 T cells between the chronically infected conjoined parabiont mice. Read More

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http://dx.doi.org/10.1073/pnas.1917298117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049149PMC
February 2020
9.809 Impact Factor

Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection.

Pathogens 2020 Feb 4;9(2). Epub 2020 Feb 4.

Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.

The replication of virus in secondary lymphoid organs is crucial for the activation of antigen-presenting cells. Balanced viral replication ensures the sufficient availability of antigens and production of cytokines, and both of which are needed for virus-specific immune activation and viral elimination. Host factors that regulate coordinated viral replication are not fully understood. Read More

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http://dx.doi.org/10.3390/pathogens9020096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168624PMC
February 2020

Wild Red Foxes () as Sentinels of Rodent-borne Hantavirus and Lymphocytic Choriomeningitis Virus in the Province of Soria, Northern Spain.

J Wildl Dis 2020 Feb 3. Epub 2020 Feb 3.

Department of Biomedicine and Biotechnology, Alcalá University, Crta Madrid-Barcelona Km 33.6, Alcaláde Henares 28801,Madrid Spain.

Three hundred and fourteen red foxes () in the province of Soria, Spain, were examined for hantavirus and lymphocytic choriomeningitis virus (LCMV) infection (and were likely to have been infected by feeding on infected rodents). Immunofluorescence and western blot assays confirmed 3.5% (11/314) to have antibodies to hantaviruses, and the immune fluorescence assay showed 2. Read More

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http://dx.doi.org/10.7589/2019-09-239DOI Listing
February 2020

Quantitative and Qualitative Analysis of Humoral Immunity Reveals Continued and Personalized Evolution in Chronic Viral Infection.

Cell Rep 2020 Jan;30(4):997-1012.e6

Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland. Electronic address:

Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution of antibody responses during acute or chronic LCMV infection, combining quantitative functional assays and time-resolved antibody repertoire sequencing. We establish that antibody responses initially converge in both infection types on a functional and repertoire level, but diverge later during chronic infection, showing increased clonal diversity, the appearance of mouse-specific persistent clones, and distinct phylogenetic signatures. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.12.088DOI Listing
January 2020

Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses.

Cell Rep 2020 Jan;30(4):1013-1026.e7

Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland. Electronic address:

Persistent viral infections subvert key elements of adaptive immunity. To compare germinal center (GC) B cell responses in chronic and acute lymphocytic choriomeningitis virus infection, we exploit activation-induced deaminase (AID) fate-reporter mice and perform adoptive B cell transfer experiments. Chronic infection yields GC B cell responses of higher cellularity than acute infections do, higher memory B cell and antibody secreting cell output for longer periods of time, a better representation of the late B cell repertoire in serum immunoglobulin, and higher titers of protective neutralizing antibodies. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996002PMC
January 2020

A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control.

J Hepatol 2020 May 15;72(5):960-975. Epub 2020 Jan 15.

Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Virology, Technical University of Munich and Helmholtz Zentrum München, Schneckenburgerstrasse 8, 81675 Munich, Germany; Institute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Ismaningerstraße 22, 81675 Munich, Germany. Electronic address:

Background & Aims: Hepatic innate immune control of viral infections has largely been attributed to Kupffer cells, the liver-resident macrophages. However, hepatocytes, the parenchymal cells of the liver, also possess potent immunological functions in addition to their known metabolic functions. Owing to their abundance in the liver and known immunological functions, we aimed to investigate the direct antiviral mechanisms employed by hepatocytes. Read More

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http://dx.doi.org/10.1016/j.jhep.2019.12.019DOI Listing
May 2020
11.336 Impact Factor

Prediction of cancer neoepitopes needs new rules.

Semin Immunol 2020 02 14;47:101387. Epub 2020 Jan 14.

Department of Immunology, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. Electronic address:

Tumors are immunogenic and the non-synonymous point mutations harbored by tumors are a source of their immunogenicity. Immunologists have long been enamored by the idea of synthetic peptides corresponding to mutated epitopes (neoepitopes) as specific "vaccines" against tumors presenting those neoepitopes in context of MHC I. Tumors may harbor hundreds of point mutations and it would require effective prediction algorithms to identify candidate neoepitopes capable of eliciting potent tumor-specific CD8 T cell responses. Read More

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http://dx.doi.org/10.1016/j.smim.2020.101387DOI Listing
February 2020

Virus-Induced Interferon Regulates the Urea Cycle.

Immunity 2019 12;51(6):975-977

Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD, USA. Electronic address:

Integrating transcriptomic, proteomic, and metabolomic data, Lercher et al. show in a mouse model of LCMV infection that type I interferon alters the expression and function of key enzymes of the urea cycle in hepatocytes. This results in altered systemic metabolism, attenuating antiviral T cell responses and ameliorating liver injury. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.11.012DOI Listing
December 2019

E3 Ligase ITCH Interacts with the Z Matrix Protein of Lassa and Mopeia Viruses and Is Required for the Release of Infectious Particles.

Viruses 2019 12 31;12(1). Epub 2019 Dec 31.

Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69365 Lyon, France.

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related, rodent-born mammarenaviruses. LASV is the causative agent of Lassa fever, a deadly hemorrhagic fever endemic in West Africa, whereas MOPV is non-pathogenic in humans. The Z matrix protein of arenaviruses is essential to virus assembly and budding by recruiting host factors, a mechanism that remains partially defined. Read More

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http://dx.doi.org/10.3390/v12010049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019300PMC
December 2019

Vaccinia Virus Vectors Targeting Peptides for MHC Class II Presentation to CD4 T Cells.

Immunohorizons 2020 01 2;4(1):1-13. Epub 2020 Jan 2.

Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239;

CD4 helper T cells play important roles in providing help to B cells, macrophages, and cytotoxic CD8 T cells, but also exhibit direct effector functions against a variety of different pathogens. In contrast to CD8 T cells, CD4 T cells typically exhibit broader specificities and undergo less clonal expansion during many types of viral infections, which often makes the identification of virus-specific CD4 T cells technically challenging. In this study, we have generated recombinant vaccinia virus (VacV) vectors that target I-A-restricted peptides for MHC class II (MHC-II) presentation to activate CD4 T cells in mice. Read More

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http://dx.doi.org/10.4049/immunohorizons.1900070DOI Listing
January 2020

Immunometabolism of infections.

Authors:
Janelle S Ayres

Nat Rev Immunol 2020 02;20(2):79-80

Molecular and Systems Physiology Lab, Gene Expression Lab and Nomis Center for Immunobiolgy and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA.

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http://dx.doi.org/10.1038/s41577-019-0266-9DOI Listing
February 2020

Case 40-2019: A 26-Year-Old Returning Traveler with Headache.

N Engl J Med 2019 Dec;381(26):2553-2560

From the Departments of Medicine (G.S.S., N.J.), Radiology (M.G.), and Pathology (M.M.S.), Massachusetts General Hospital, and the Departments of Medicine (G.S.S., N.J.), Radiology (M.G.), and Pathology (M.M.S.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc1904042DOI Listing
December 2019

Loss of Resistance to Mousepox during Chronic Lymphocytic Choriomeningitis Virus Infection Is Associated with Impaired T-Cell Responses and Can Be Rescued by Immunization.

J Virol 2020 Feb 14;94(5). Epub 2020 Feb 14.

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

It is well established that chronic viral infections can cause immune suppression, resulting in increased susceptibility to other infectious diseases. However, the effects of chronic viral infection on T-cell responses and vaccination against highly pathogenic viruses are not well understood. We have recently shown that C57BL/6 (B6) mice lose their natural resistance to wild-type (WT) ectromelia virus (ECTV) when chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13). Read More

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http://dx.doi.org/10.1128/JVI.01832-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022357PMC
February 2020
4.439 Impact Factor

PD-1 Expression during Acute Infection Is Repressed through an LSD1-Blimp-1 Axis.

J Immunol 2020 Jan 6;204(2):449-458. Epub 2019 Dec 6.

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and

During prolonged exposure to Ags, such as chronic viral infections, sustained TCR signaling can result in T cell exhaustion mediated in part by expression of programmed cell death-1 (PD-1) encoded by the gene. In this study, dynamic changes in histone H3K4 modifications at the locus during ex vivo and in vivo activation of CD8 T cells suggested a potential role for the histone H3 lysine 4 demethylase LSD1 in regulating PD-1 expression. CD8 T cells lacking LSD1 expressed higher levels of mRNA following ex vivo stimulation as well as increased surface levels of PD-1 during acute, but not chronic, infection with lymphocytic choriomeningitis virus (LCMV). Read More

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http://dx.doi.org/10.4049/jimmunol.1900601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946872PMC
January 2020

Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1 Stem-like CD8 T Cells during Chronic Infection.

Immunity 2019 12 3;51(6):1043-1058.e4. Epub 2019 Dec 3.

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30033, USA. Electronic address:

T cell dysfunction is a characteristic feature of chronic viral infection and cancer. Recent studies in chronic lymphocytic choriomeningitis virus (LCMV) infection have defined a PD-1 Tcf-1 CD8 T cell subset capable of self-renewal and differentiation into more terminally differentiated cells that downregulate Tcf-1 and express additional inhibitory molecules such as Tim3. Here, we demonstrated that expression of the glycoprotein CD101 divides this terminally differentiated population into two subsets. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920571PMC
December 2019