Virus associated innate immunity in liver.

Abstract

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.

• Authors: Tatsuya Kanto
• Journal: Frontiers in bioscience : a journal and virtual library (Front Biosci) Vol. 13 Pg. 6183-92 (May 01 2008) ISSN: 1093-9946 [Print] United States
• PMID: 18508652 (Publication Type: Journal Article, Review)

Chemical References

• Toll-Like Receptors

Topics

• Dendritic Cells (classification, immunology)
• Hepatitis C (immunology)
• Hepatitis, Viral, Human (immunology)
• Humans
• Immunity, Innate
• Killer Cells, Natural (immunology)
• Liver (immunology, virology)
• Lymphocyte Subsets (immunology)
• T-Lymphocytes (immunology)
• Toll-Like Receptors (physiology)