Impaired cytokine response in myeloid dendritic cells in chronic hepatitis C virus infection regardless of enhanced expression of Toll-like receptors and retinoic acid inducible gene-I
Version of Record online: 21 APR 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Medical Virology
Volume 80, Issue 6, pages 980–988, June 2008
How to Cite
Miyazaki, M., Kanto, T., Inoue, M., Itose, I., Miyatake, H., Sakakibara, M., Yakushijin, T., Kakita, N., Hiramatsu, N., Takehara, T., Kasahara, A. and Hayashi, N. (2008), Impaired cytokine response in myeloid dendritic cells in chronic hepatitis C virus infection regardless of enhanced expression of Toll-like receptors and retinoic acid inducible gene-I. J. Med. Virol., 80: 980–988. doi: 10.1002/jmv.21174
- Issue online: 21 APR 2008
- Version of Record online: 21 APR 2008
- Manuscript Accepted: 5 FEB 2008
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labor and Welfare of Japan
- chronic hepatitis C;
- myeloid dendritic cell;
- innate immunity;
Dendritic cells utilize various sets of Toll-like receptors (TLR) or cytosolic sensors to detect pathogens and evoke immune responses. In patients with hepatitis C virus (HCV) infection, a higher prevalence of various infectious diseases is reported; suggesting that innate immunity against pathogens is impaired. The aim of this study was to clarify whether the TLR and retinoic acid inducible gene-I (RIG-I) system in myeloid dendritic cells is preserved or not in chronic HCV infection. The expression of TLRs, RIG-I and its relatives were compared in myeloid dendritic cells between 39 patients and 52 healthy volunteers. The induction of type-I interferon (IFN) and inflammatory cytokines was examined in response to agonists for TLR2 (palmitoyl-3-cysteine-serine-lysine-4), TLR3/RIG-I (polyinosine–polycytidylic acid) or TLR4 (lipopolysaccharide). The relative expressions of TLR2, TLR4, RIG-I, and LGP2 from the patients were significantly higher than those from the volunteers, whereas TLR3 and MDA-5 expressions did not differ. In search for factors regulating TLR/RIG-I expression, it was shown that IFN-α, polyinosine–polycytidylic acid and lipopolysaccharide induced TLR3, TLR4 and RIG-I, but TNF-α, HCV core or HCV non-structural proteins did not. For the functional analyses, myeloid dendritic cells from the patients induced significantly less amounts of IFN-β, TNF-α and IL-12p70 in response to polyinosine–polycytidylic acid or lipopolysaccharide. It is noteworthy that the expression of TRIF and TRAF6, which are essential adaptor molecules transmitting TLR3 or TLR4-dependent signals, is reduced in the patients. Thus, innate cytokine responses in myeloid dendritic cells are impaired regardless of enhanced expressions of TLR2, TLR4, and RIG-I in HCV infection. J. Med. Virol. 80:980–988, 2008. © 2008 Wiley-Liss, Inc.