Toll-like receptor (TLR)-2 promotes both mouse hepatitis virus (MHV) replication and inflammatory responses in hepatocytes leading to fulminant hepatitis.
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1
Université du Québec à Montréal, Sciences Biologiques, Canada
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2
Université de Rennes 1, IRSET-INSERM U 10856, France
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.
Acknowledgements
This work has been funded by NSERC-Canada.
Keywords:
Liver,
TLR2,
Coronavirus,
cytokines/chemokines,
Hepatocytes
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Bleau
C,
Burnette
M,
Jacques
A,
Piquet-Pellorce
C,
Samson
M and
Lamontagne
L
(2013). Toll-like receptor (TLR)-2 promotes both mouse hepatitis virus (MHV) replication and inflammatory responses in hepatocytes leading to fulminant hepatitis..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00648
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Lucie Lamontagne, Université du Québec à Montréal, Sciences Biologiques, Montréal, HJ3C 3P8, Canada, lamontagne.lucie@uqam.ca