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Toll-like receptor (TLR)-2 promotes both mouse hepatitis virus (MHV) replication and inflammatory responses in hepatocytes leading to fulminant hepatitis.

Abstract : Acute viral hepatitis results from an inefficient innate immune response to clear the virus and a delayed immune adaptive response. Murine hepatitis virus (MHV) infection represents a unique animal model to identify new escape mechanisms in liver of innate immune responses. The objective of this study was to identify early disorders in TLRs, helicases, cytokines and chemokines favoring the development of a fulminant hepatitis. Groups of C57BL/6 WT and TLR2-/- mice were infected with highly hepatotropic MHV3 and/or weakly hepatotropic MHV-A59 viruses. Histopathological analysis of liver and mRNA expression levels of viral nucleoprotein, viral sensors, interferons, cytokines and chemokines assessed by RT-qPCR were done in the first 3 days of infection. The results showed that liver damages, viral replication and mRNA levels of TLR-2, TLR-3, RIG-1, MDA-5, IL-33, IFN-b, CXCL1, CXCL9, CXCL-10, CXCL-11, CCL3, CCL5, IL-6 and TNF-a increased higher or appeared sooner in MHV3-infected WT than in MHV-A59 and TLR2-/- mice. To address the role of hepatocytes in TLR2-dependent viral replication and innate immune factors, in vitro viral infections were performed on FL83B cells. The results showed that viral replication and mRNA levels of TLR-2 and IL-6 occurred sooner than those of other innate immune parameters. Moreover, blockade of TLR-2 by siRNA decreased IFN-b, TNF-a, CXCL-1, CXCL-10 and CCL-2 expression in infected hepatocytes and also inhibited the viral replication of MHV-A59, and at a lesser extent of MHV3, suggesting that TLR-2 signaling promotes simultaneously the viral replication and the production of innate immune factors in hepatocytes, exacerbating viral hepatitis.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118155
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Submitted on : Wednesday, February 18, 2015 - 3:31:32 PM
Last modification on : Saturday, June 6, 2020 - 6:16:02 AM

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Christian Bleau, Mélanie Burnette, Alexandre Jacques, Claire Piquet-Pellorce, Michel Samson, et al.. Toll-like receptor (TLR)-2 promotes both mouse hepatitis virus (MHV) replication and inflammatory responses in hepatocytes leading to fulminant hepatitis.. 15th International Congress of Immunology (ICI), Aug 2013, Milan, Italy. ⟨10.3389/conf.fimmu.2013.02.00648⟩. ⟨hal-01118155⟩

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