Virus associated innate immunity in liver.
Dendritic cells (DCs) sense virus via toll-like receptors (TLR) or retinoic acid inducible gene-I (RIG-I) and evoke a cascade of immune reactions. In myeloid DC (MDC) from hepatitis C virus (HCV)-infected patients, the levels of TLR/RIG-I-mediated IFN-beta or TNF-alfa induction are lower than those in uninfected donors, suggesting that their signal transduction in MDC is impaired. Dendritic cells in HCV infection are unresponsive to interferon (IFN)-alfa, thus failing to enhance MHC class-I related chain A/B and subsequent NK cell activation. Alternatively, NK cells from the patients down-regulate DC in the presence of HLA-E-expressing hepatocytes by secreting IL-10 and TGF-beta1. Such functional alteration of NK cells in HCV infection is ascribed to the enhanced expression of NKG2A/CD94. Activated NKT cells from the patients produce higher levels of IL-13 but comparable IFN-gamma with those from controls, showing their bias to Th2-type. In pegylated IFN-alfa/ribavirin therapy for chronic hepatitis C, improved DC function is related with successful HCV eradication. In conclusion, cross-talks among DCs and innate lymphocytes are critical in shaping immune response against HCV, either spontaneously or therapeutically.
Kanto
Tatsuya
T
Department of Gastroenterology, Osaka University Graduate School of Medicine, Suita, Japan. kantot@gh.med.osaka-u.ac.jp
D003713:Dendritic Cells / Q000145:classification / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D006525:Hepatitis, Viral, Human / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000821:virology*; D016131:Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology
D051193:Toll-Like Receptors