Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
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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.