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Interferon type I immunity

S L Semple, N T K Vo, S J Poynter, M Li, D D Heath, S J DeWitte-Orr, B Dixon
Despite increased global interest in Chinook salmon aquaculture, little is known of their viral immune defenses. This study describes the establishment and characterization of a continuous cell line derived from Chinook salmon spleen, CHSS, and its use in innate immune studies. Optimal growth was seen at 14-18 °C when grown in Leibovitz's L-15 media with 20% fetal bovine serum. DNA analyses confirmed that CHSS was Chinook salmon and genetically different from the only other available Chinook salmon cell line, CHSE-214...
August 14, 2018: Developmental and Comparative Immunology
Vanessa D'Urbano, Elisa De Crignis, Maria Carla Re
Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus...
August 16, 2018: Current HIV Research
Angela Lombardi, Effie Tsomos, Sara S Hammerstad, Yaron Tomer
IFNα is a cytokine essential to a vast array of immunologic processes. Its induction early in the innate immune response provides a priming mechanism that orchestrates numerous subsequent pathways in innate and adaptive immunity. Despite its beneficial effects in viral infections IFNα has been reported to be associated with several autoimmune diseases including autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, primary biliary cholangitis, and recently emerged as a major cytokine that triggers Type 1 Diabetes...
August 13, 2018: Journal of Autoimmunity
Elisabeth Lang, Vitaly I Pozdeev, Prashant V Shinde, Haifeng C Xu, Balamurugan Sundaram, Yuan Zhuang, Gereon Poschmann, Jun Huang, Kai Stühler, Aleksandra A Pandyra, Verena Keitel, Dieter Häussinger, Karl S Lang, Philipp A Lang
Immune responses are critical for defense against pathogens. However, prolonged viral infection can result in defective T cell immunity, leading to chronic viral infection. We studied immune activation in response to arenavirus infection during cholestasis using bile duct ligation (BDL). We monitored T cell responses, virus load and liver pathology markers after infection with lymphocytic choriomeningitis virus (LCMV). BDL mice failed to induce protective anti-viral immunity against LCMV and consequently exhibited chronic viral infection...
August 15, 2018: Scientific Reports
Michael E Lindquist, Xiankun Zeng, Louis A Altamura, Sharon P Daye, Korey L Delp, Candace Blancett, Kayla M Coffin, Jeffrey W Koehler, Susan Coyne, Charles J Shoemaker, Aura R Garrison, Joseph W Golden
Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe hepatic injury in humans. However, the mechanism(s) causing this damage are poorly characterized. CCHFV produces an acute disease, including liver damage, in mice lacking type I interferon signaling (IFN-I) either due to STAT-1 gene deletion or disruption of the IFN-I receptor 1 gene. Here, we explored CCHFV-induced liver pathogenesis in mice using an antibody to disrupt IFN-I signaling. When IFN-I blockade was induced within 24 h post-exposure to CCHFV, mice developed severe disease with greater than 95% mortality by six days post-exposure...
August 15, 2018: Journal of Virology
Jessalyn M Hadfield, Elizabeth C Bowdridge, Ida Holásková, Ted H Elsasser, Robert A Dailey
Innate immune response to a lipopolysaccharide (LPS) challenge varies among sheep breeds. How different breeds respond to bacterial infections impacts management practices of sheep producers. Hence, clinical response, acute-phase response, and gene expression of pro- and anti-inflammatory markers in peripheral white blood cells (WBCs) were examined after an LPS challenge in Dorset and Suffolk ewes. Ewes received either PBS or 2.5 µg/kg LPS (i.v.) 4 to 5 d after onset of synchronized estrus. Blood was collected via jugular venipuncture intermittently for 24 h to determine WBC counts...
August 9, 2018: Journal of Animal Science
Xinhua Zhu, Ke Liu, Jialin Wang, Haisen Peng, Qibin Pan, Shuhong Wu, Yinli Jiang, Yuehui Liu
The present study aimed to investigate the effects of C‑C chemokine receptor type 3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3‑/‑ BALB/c mice to establish an AR model. The mice were divided into four groups: i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3‑/‑CG) and iv) AR model with CCR3 knockout (CCR3‑/‑AR). Histological sections of nasal mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3 knockout suppressed the invasion of inflammatory cells and relieved the damage of nasal mucosae...
August 10, 2018: Molecular Medicine Reports
Hongjun Huang, Qingqing Xiong, Ning Wang, Ruoyu Chen, Hua Ren, Stefan Siwko, Honghui Han, Mingyao Liu, Min Qian, Bing Du
G protein-coupled receptor 54 (GPR54), the key receptor for the neuropeptide hormone kisspeptin, plays essential roles in regulating puberty development and cancer metastasis. However, its role in the antiviral innate immune response is unknown. We report that virus-induced type I interferon (IFN-I) production was significantly enhanced in Gpr54 -deficient cells and mice and resulted in restricted viral replication. We found a marked increase of kisspeptin in mouse serum during viral infection, which, in turn, impaired IFN-I production and antiviral immunity through the GPR54/calcineurin axis...
August 2018: Science Advances
Shawn T Beug, Stephanie J Pichette, Martine St-Jean, Janelle Holbrook, Danielle E Walker, Eric C LaCasse, Robert G Korneluk
Smac mimetic compounds (SMCs) are anti-cancer drugs that antagonize Inhibitor of Apoptosis proteins, which consequently sensitize cancer cells to death in the presence of proinflammatory ligands such as tumor necrosis factor alpha (TNF-α). SMCs synergize with the attenuated oncolytic vesicular stomatitis virus (VSVΔ51) by eliciting an innate immune response, which is dependent on the endogenous production of TNF-α and type I interferon. To improve on this SMC-mediated synergistic response, we generated TNF-α-armed VSVΔ51 to produce elevated levels of this death ligand...
September 28, 2018: Molecular Therapy Oncolytics
GuanQun Liu, Yao Lu, Sathya N Thulasi Raman, Fang Xu, Qi Wu, Zhubing Li, Robert Brownlie, Qiang Liu, Yan Zhou
The nucleus represents a cellular compartment where the discrimination of self from non-self nucleic acids is vital. While emerging evidence establishes a nuclear non-self DNA sensing paradigm, the nuclear sensing of non-self RNA, such as that from nuclear-replicating RNA viruses, remains unexplored. Here, we report the identification of nuclear-resident RIG-I actively involved in nuclear viral RNA sensing. The nuclear RIG-I, along with its cytoplasmic counterpart, senses influenza A virus (IAV) nuclear replication leading to a cooperative induction of type I interferon response...
August 10, 2018: Nature Communications
Matteo Rossi, Nicolas Fasel
In nature, humans infected with protozoan parasites can encounter viruses, which could alter their host immune response. The impact of viruses on human parasitic diseases remains largely unexplored due to the highly sterilized environment in experimental studies and the difficulty to draw a correlation between co-infection and pathology. Recent studies show that viral infections exacerbate pathology and promote dissemination of some Leishmania infections, based on a hyper-inflammatory reaction driven by type I interferons...
August 7, 2018: Current Opinion in Microbiology
Mingchun Gao, Yongli Guo, Jiwen Du, Zhifeng Song, Xiuxin Luo, Junwei Wang, Wenyu Han
IFN-kappa (IFN-κ) is a type I IFN expressed by keratinocytes, monocytes and dendritic cells with important roles during the innate immune response period. This research was conducted to elaborate the evolution and characteristics of IFN-κ in poultry. Chicken IFN-κ is located on the sex-determining Z chromosome, which is greatly different from mammals. Poultry IFN-κ cluster together in a species-specific manner through positive selection pressure and share only 19-33% homology with mammalian IFN-κ and poultry other type I IFN...
August 6, 2018: Developmental and Comparative Immunology
Nandini Sen, Phillip Sung, Arjun Panda, Ann M Arvin
Both type I and type II interferons (IFNs) have been implicated in the host defense against varicella zoster virus (VZV), a common human herpesvirus that causes varicella and zoster. The purpose of this study was to compare their contributions to the control of VZV replication, to identify the signaling pathways that are critical for mediating their antiviral activity, and to define mechanisms by which the virus counteracts their effects. IFNγ was much more potent than IFNα in blocking VZV infection, which was associated with a differential induction of the interferon regulatory factor (IRF) proteins, IRF1 and IRF9, respectively...
August 8, 2018: Journal of Virology
Sang-Cheol Bae, Young Ho Lee
Our purpose was to identify differentially expressed (DE) genes and biological processes associated with gene expression changes in systemic lupus erythematosus (SLE). We performed a meta-analysis using the INMEX program (integrative meta-analysis of expression data) on publicly available microarray Genetic Expression Omnibus (GEO) datasets of peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. We performed Gene Ontology (GO) enrichment analysis by using hypergeometric tests. In total, five comparisons (2 B cells, 2 CD4 T cells, and 1 myeloid cell) from two GEO datasets containing 51 cases and 46 controls were included in the meta-analysis...
July 30, 2018: Cellular and Molecular Biology
Xiaomin Guo, Huan Wang, Yang Li, Xiaopeng Leng, Weiwei Huang, Yanbing Ma, Tao Xu, Xiaopeng Qi
The commercial transfection reagent Lipofectamine has been widely used for cytoplasmic delivery of nucleic acids and for cytosolic engagement with intracellular innate immune sensors to trigger type I interferon (IFN) production. However, the effect of Lipofectamine alone on type I IFN response has not been studied in detail. Here, we show that Lipofectamine induced type I IFN signaling in both RAW 264.7 macrophage-like cells and primary bone marrow-derived macrophages. Type I IFN induction was dependent on IRF3 and IRF7 and partially required the TIR-domain-containing adapter-inducing interferon-β...
August 6, 2018: Immunology and Cell Biology
Paoline Laurent, Vanja Sisirak, Estibaliz Lazaro, Christophe Richez, Pierre Duffau, Patrick Blanco, Marie-Elise Truchetet, Cécile Contin-Bordes
Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by three interconnected hallmarks (i) vasculopathy, (ii) aberrant immune activation, and (iii) fibroblast dysfunction leading to extracellular matrix deposition and fibrosis. Blocking or reversing the fibrotic process associated with this devastating disease is still an unmet clinical need. Although various components of innate immunity, including macrophages and type I interferon, have long been implicated in SSc, the precise mechanisms that regulate the global innate immune contribution to SSc pathogenesis remain poorly understood...
2018: Frontiers in Immunology
Jacob T Beaver, Nadia Lelutiu, Rumi Habib, Ioanna Skountzou
Zika virus (ZIKV) became a public health emergency of global concern in 2015 due to its rapid expansion from French Polynesia to Brazil, spreading quickly throughout the Americas. Its unexpected correlation to neurological impairments and defects, now known as congenital Zika syndrome, brought on an urgency to characterize the pathology and develop safe, effective vaccines. ZIKV genetic analyses have identified two major lineages, Asian and African, which have undergone substantial changes during the past 50 years...
2018: Frontiers in Immunology
Yanyan Zheng, Qingxiang Liu, Yaoxing Wu, Ling Ma, Zhenzhen Zhang, Tao Liu, Shouheng Jin, Yuanchu She, Yi-Ping Li, Jun Cui
Viral infection triggers host innate immune responses, which primarily include the activation of type I interferon (IFN) signaling and inflammasomes. Here, we report that Zika virus (ZIKV) infection triggers NLRP3 inflammasome activation, which is further enhanced by viral non-structural protein NS1 to benefit its replication. NS1 recruits the host deubiquitinase USP8 to cleave K11-linked poly-ubiquitin chains from caspase-1 at Lys134, thus inhibiting the proteasomal degradation of caspase-1. The enhanced stabilization of caspase-1 by NS1 promotes the cleavage of cGAS, which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection...
July 31, 2018: EMBO Journal
Marc-Antoine de La Vega, Jocelyne Piret, Bryan D Griffin, Chantal Rhéaume, Marie-Christine Venable, Julie Carbonneau, Christian Couture, Raquel das Neves Almeida, Roland R Tremblay, Kelly G Magalhães, Young K Park, Christine C Roberts, Joel N Maslow, Niranjan Y Sardesai, J Joseph Kim, Kar Muthumani, David B Weiner, Gary P Kobinger, Guy Boivin
Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice. Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J...
July 24, 2018: Journal of Infectious Diseases
Dana Mitchell, Sreenivasulu Chintala, Mahua Dey
Plasmacytoid dendritic cells (pDCs) comprise a subset of dendritic cells characterized by their ability to produce large amount of type I interferon (IFN-I/α). Originally recognized for their role in modulating immune responses to viral stimulation, growing interest has been directed toward their contribution to tumorigenesis. Under normal conditions, Toll-like receptor (TLR)-activated pDCs exhibit robust IFN-α production and promote both innate and adaptive immune responses. In cancer, however, pDCs demonstrate an impaired response to TLR7/9 activation, decreased or absent IFN-α production and contribute to the establishment of an immunosuppressive tumor microenvironment...
September 15, 2018: Journal of Neuroimmunology
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