22,869 results match your criteria interferon stimulated

The Dual Function of KDM5C in Both Gene Transcriptional Activation and Repression Promotes Breast Cancer Cell Growth and Tumorigenesis.

Adv Sci (Weinh) 2021 05 18;8(9):2004635. Epub 2021 Feb 18.

State Key Laboratory of Cellular Stress Biology Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical Sciences Xiamen University Xiang'an South Road Xiamen Fujian 361102 China.

Emerging evidence suggested that epigenetic regulators can exhibit both activator and repressor activities in gene transcriptional regulation and disease development, such as cancer. However, how these dual activities are regulated and coordinated in specific cellular contexts remains elusive. Here, it is reported that KDM5C, a repressive histone demethylase, unexpectedly activates estrogen receptor alpha (ER)-target genes, and meanwhile suppresses type I interferons (IFNs) and IFN-stimulated genes (ISGs) to promote ER-positive breast cancer cell growth and tumorigenesis. Read More

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The Intestinal Microbiome Primes Host Innate Immunity against Enteric Virus Systemic Infection through Type I Interferon.

mBio 2021 May 11;12(3). Epub 2021 May 11.

Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China

Intestinal microbiomes are of vital importance in antagonizing systemic viral infection. However, very little literature has shown whether commensal bacteria play a crucial role in protecting against enteric virus systemic infection from the aspect of modulating host innate immunity. In the present study, we utilized an enteric virus, encephalomyocarditis virus (EMCV), to inoculate mice treated with phosphate-buffered saline (PBS) or given an antibiotic cocktail (Abx) orally or intraperitoneally to examine the impact of microbiota depletion on virulence and viral replication Microbiota depletion exacerbated the mortality, neuropathogenesis, viremia, and viral burden in brains following EMCV infection. Read More

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Genetic predisposition in the 2'-5'A pathway in the development of type 1 diabetes: potential contribution to dysregulation of innate antiviral immunity.

Diabetologia 2021 May 11. Epub 2021 May 11.

The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen, Denmark.

Aims/hypothesis: The incidence of type 1 diabetes is increasing more rapidly than can be explained by genetic drift. Viruses may play an important role in the disease, as they seem to activate the 2'-5'-linked oligoadenylate (2'-5'A) pathway of the innate antiviral immune system. Our aim was to investigate this possibility. Read More

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CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection.

bioRxiv 2021 May 4. Epub 2021 May 4.

SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts viral burden in the lung. Read More

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Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity.

Nat Cell Biol 2021 May 10. Epub 2021 May 10.

Université de Paris, INSERM U976, Paris, France.

COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. Read More

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Transcriptome analysis reveals a complex response to the RGNNV/SJNNV reassortant Nervous Necrosis Virus strain in sea bream larvae.

Fish Shellfish Immunol 2021 May 7. Epub 2021 May 7.

Department of Comparative Biomedicine and Food Science, University of Padova, Viale Dell'Università, 16 35020, Legnaro, PD, Italy.

The gilthead sea bream (Sparus aurata) is a marine fish of great importance for Mediterranean aquaculture. This species has long been considered resistant to Nervous Necrosis Virus (NNV), an RNA virus that causes massive mortalities in several farmed fish animals. However, the recent appearance of RGNNV/SJNNV reassortant strains started to pose a serious threat to sea bream hatcheries, as it is able to infect larvae and juveniles of this species. Read More

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Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20.

EMBO Rep 2021 May 9:e49568. Epub 2021 May 9.

Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.

Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Interferons can diminish HBV cccDNA via APOBEC3-mediated deamination. Here, we show that overexpression of APOBEC3A alone is not sufficient to reduce HBV cccDNA that requires additional treatment of cells with interferon indicating involvement of an interferon-stimulated gene (ISG) in cccDNA degradation. Read More

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Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics.

Lancet Microbe 2021 May 4;2(5):e210-e218. Epub 2021 Mar 4.

Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: The COVID-19 agent, SARS-CoV-2, is conspecific with SARS-CoV, the causal agent of the severe acute respiratory syndrome epidemic in 2002-03. Although the viruses share a completely homologous repertoire of proteins and use the same cellular entry receptor, their transmission efficiencies and pathogenetic traits differ. We aimed to compare interferon antagonism by SARS-CoV and SARS-CoV-2. Read More

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Reduced A-to-I editing of endogenous Alu RNAs in lung after SARS-CoV-2 infection.

Curr Res Immunol 2021 30;2:52-59. Epub 2021 Apr 30.

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37212, USA.

Due to potential severity of disease caused by SARS-CoV-2 infection, it is critical to understand both mechanisms of viral pathogenesis as well as diversity of host responses to infection. Reduced A-to-I editing of endogenous double-stranded RNAs (dsRNAs), as a result of inactivating mutations in , produces one form of Aicardi-Goutières Syndrome, with an immune response similar to an anti-viral response. By analyzing whole genome RNA sequencing data, we find reduced levels of A-to-I editing of endogenous Alu RNAs in normal human lung cells after infection by SARS-CoV-2 as well as in lung biopsies from patients with SARS-CoV-2 infections. Read More

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Crosstalk Between SUMO and Ubiquitin-Like Proteins: Implication for Antiviral Defense.

Front Cell Dev Biol 2021 21;9:671067. Epub 2021 Apr 21.

Institute for Research in Immunology and Cancer, Montréal, QC, Canada.

Interferon (IFN) is a crucial first line of defense against viral infection. This cytokine induces the expression of several IFN-Stimulated Genes (ISGs), some of which act as restriction factors. Upon IFN stimulation, cells also express ISG15 and SUMO, two key ubiquitin-like (Ubl) modifiers that play important roles in the antiviral response. Read More

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BTLA Expression and Function Are Impaired on SLE B Cells.

Front Immunol 2021 22;12:667991. Epub 2021 Apr 22.

Department of Rheumatology and Clinical Immunology, Charité- Universitätsmedizin Berlin, Berlin, Germany.

B- and T-lymphocyte attenuator (BTLA/CD272) is an inhibitory checkpoint molecule expressed on T and B cells. Prior studies reported defective function of BTLA by T cells in patients with systemic lupus erythematosus (SLE), whereas nothing is known about its role on B cells in SLE, a disease with various B cell abnormalities. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors (HD) and 34 SLE patients were stained for BTLA and its expression on B cells was assessed. Read More

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SNPs of the IFNL favour spontaneous clearance of HCV infection in children.

Pediatr Res 2021 May 8. Epub 2021 May 8.

Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy.

Background: Both spontaneous and treatment-induced clearance of hepatitis C virus (HCV) in adults have been associated with genetic polymorphisms in the interferon-λ genes. The aim of the present study was to confirm the association between the rs12979860 and evaluate the association between the rs368234815 and the rs4803217 single-nucleotide polymorphisms (SNPs) of the interferon-λ genes and the outcome of the infection in children.

Methods: Alleles and genotypes frequencies of 32 children, who presented spontaneous clearance of the virus and 135 children, with viral persistence were compared with ethnically matched controls obtained from the 1000 Genomes Project and the International HapMap Project databases. Read More

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Interferon- and STING-independent induction of type I interferon stimulated genes during fractionated irradiation.

J Exp Clin Cancer Res 2021 May 8;40(1):161. Epub 2021 May 8.

Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.

Background: Improvement of radiotherapy efficacy requires better insight in the dynamic responses that occur during irradiation. Here, we aimed to identify the molecular responses that are triggered during clinically applied fractionated irradiation.

Methods: Gene expression analysis was performed by RNAseq or microarray analysis of cancer cells or xenograft tumors, respectively, subjected to 3-5 weeks of 5 × 2 Gy/week. Read More

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Upregulated expression of ferret Interferon-Inducible Transmembrane genes by IFN-α and influenza virus infection.

J Virol 2021 May 5. Epub 2021 May 5.

Commonwealth Science and Industrial Research Organisation, Health & Biosecurity, Australian Centre for Disease Preparedness, East Geelong, Victoria, Australia.

The current fears of a future influenza pandemic have resulted in an increased emphasis on the development and testing of novel therapeutic strategies against the virus. Fundamental to this is the ferret model of influenza infection, critical in examining pathogenesis and treatment. Nevertheless, a precise evaluation of the efficacy of any treatment strategy in ferrets is reliant on understanding the immune response in this model. Read More

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Potential role of IFN-α in COVID-19 patients and its underlying treatment options.

Appl Microbiol Biotechnol 2021 May 5. Epub 2021 May 5.

Department of Pathology, Yale School of Medicine, New Haven, CT, 06511, USA.

The coronavirus disease (COVID-19) caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. Given that this contagious viral outbreak is still unfolding, it is urgent to understand the pathogenesis of SARS-CoV-2 infection and explore effective treatments to protect patients from developing a severe illness related to COVID-19. Recently, IFN-α has been considered a potential therapeutic strategy to treat COVID-19 disease, mainly because the innate immune system rapidly produces IFN-α as the first line of defense to combat viral infections. Read More

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The Zinc Finger Antiviral Protein ZAP Restricts Human Cytomegalovirus and Selectively Binds and Destabilizes Viral / Transcripts.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Viral Immune Modulation Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany

Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonizes several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is less well understood. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. Read More

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A Quorum Sensing System Enables Suppression of Innate Immunity.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA

Some bacterial pathogens utilize cell-cell communication systems, such as quorum sensing (QS), to coordinate genetic programs during host colonization and infection. The human-restricted pathosymbiont (group A streptococcus [GAS]) uses the Rgg2/Rgg3 QS system to modify the bacterial surface, enabling biofilm formation and lysozyme resistance. Here, we demonstrate that innate immune cell responses to GAS are substantially altered by the QS status of the bacteria. Read More

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T-cell response to phytohemagglutinin in the interferon-γ release assay as a potential biomarker for the response to immune checkpoint inhibitors in patients with non-small cell lung cancer.

Thorac Cancer 2021 May 4. Epub 2021 May 4.

Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Background: Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T-cell response, and interferon-γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon-γ-releasing peripheral T cells after phytohemagglutinin stimulation in the interferon-γ release assay might act as a biomarker for the response of non-small cell lung cancer to immune checkpoint inhibitor treatment. Read More

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Analysis of specific antibody and cellular immune response to first-dose measles vaccine Edmonston-Zagreb in 9-month-old infants.

Allergol Immunopathol (Madr) 2021 1;49(3):193-201. Epub 2021 May 1.

Bio Farma, Pasteur Street No. 28, Bandung 40161, West Java, Indonesia.

Background: Measles vaccinations have been suggested to provide immune protection and decreased measles incidence. However, there was a limited study evaluating how the measles vaccine elicits specific immune responses.

Objective: This study aimed to evaluate both humoral and cellular immunity to first-dose measles vaccine Edmonston-Zagreb (EZ) in 9-month-old Indonesian infants. Read More

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Management of SARS-CoV-2 Infection: Key Focus in Macrolides Efficacy for COVID-19.

Front Med (Lausanne) 2021 14;8:642313. Epub 2021 Apr 14.

Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Macrolides (e.g., erythromycin, fidaxomicin, clarithromycin, and azithromycin) are a class of bacteriostatic antibiotics commonly employed in medicine against various gram-positive and atypical bacterial species mostly related to respiratory tract infections, besides they possess anti-inflammatory and immunomodulatory effects. Read More

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SARS-CoV-2 Infection Induces Psoriatic Arthritis Flares and Enthesis Resident Plasmacytoid Dendritic Cell Type-1 Interferon Inhibition by JAK Antagonism Offer Novel Spondyloarthritis Pathogenesis Insights.

Front Immunol 2021 15;12:635018. Epub 2021 Apr 15.

Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, United Kingdom.

Objective: Bacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares. Read More

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Bile acids LCA and CDCA inhibited porcine deltacoronavirus replication in vitro.

Vet Microbiol 2021 Apr 28;257:109097. Epub 2021 Apr 28.

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, College of Food, Agricultural and Environmental Sciences, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH, USA. Electronic address:

Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes gastroenteritis in pigs and no vaccines or antiviral drugs are available. Bile acids are active factors in intestines and influence the replication of enteric viruses. Currently, the role of bile acids on PDCoV replication is unknown. Read More

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HOIL-1-catalysed ester-linked ubiquitylation restricts IL-18 signaling in cytotoxic T cells but promotes TLR signalling in macrophages.

FEBS J 2021 May 1. Epub 2021 May 1.

MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life sciences, University of Dundee, UK.

The atypical E3 ligase HOIL-1 forms ester bonds between ubiquitin and serine/threonine residues in proteins, but the physiological roles of this unusual modification are unknown. We now report that IL-18 signalling leading to the production of interferon γ (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is enhanced in cytotoxic T cells from knock-in mice expressing the E3 ligase-inactive HOIL-1[C458S] mutant, demonstrating that the formation of HOIL-1-catalysed ester-linked ubiquitin bonds restricts the activation of this pathway. We show that the interaction of IRAK2 with TRAF6 is required for IL-18-stimulated IFN-γ and GM-CSF production, and that the increased production of these cytokines in cytotoxic T cells from HOIL-1[C458S] mice correlates with an increase in both the number and size of the Lys63/Met1-linked hybrid ubiquitin chains attached to IRAK2 in these cells. Read More

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Functional landscape of SARS-CoV-2 cellular restriction.

Mol Cell 2021 Apr 13. Epub 2021 Apr 13.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA; The Tisch Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA.

A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. Read More

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Inducible knockout of Clec16a in mice results in sensory neurodegeneration.

Sci Rep 2021 Apr 29;11(1):9319. Epub 2021 Apr 29.

The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.

CLEC16A has been shown to play a role in autophagy/mitophagy processes. Additionally, genetic variants in CLEC16A have been implicated in multiple autoimmune diseases. We generated an inducible whole-body knockout, Clec16a mice, to investigate the loss of function of CLEC16A. Read More

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Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

Department of Dermatology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea.

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. Read More

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Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 514400, China.

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. Read More

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Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures.

Viruses 2021 04 28;13(5). Epub 2021 Apr 28.

CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, 46 allée d'Italie, 69007 Lyon, France.

The order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Read More

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Induction of during the Crosstalk between Antigen Presenting Like-Cells MHCIICD83 and Splenocytes CD4IgM in Rainbow Trout.

Biology (Basel) 2021 Apr 13;10(4). Epub 2021 Apr 13.

Grupo de Marcadores Inmunológicos en Organismos Acuáticos, Laboratorio de Genética e Inmunología Molecular, Instituto de Biología, Pontificia Universidad Católica de Valparaíso, 2340000 Valparaíso, Chile.

In fish, the spleen is one of the major immune organs in the animal, and the splenocytes could play a key role in the activation and modulation of the immune response, both innate and adaptive. However, the crosstalk between different types of immune cells in the spleen has been poorly understood. In this work, an in vitro strategy is carried out to obtain and characterize mononuclear splenocytes from rainbow trout, using biomarkers associated with lymphocytes (CD4 and IgM) and antigen-presenting cells (CD83 and MHC II). Read More

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Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. Read More

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