Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV)

Sensors

Masato Nakai¹  Hiroyuki Oshiumi¹  Kenji Funami¹  Masaaki Okamoto¹  Misako Matsumoto¹  Tsukasa Seya¹  Naoya Sakamoto² 

[1] Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan; E-Mails:;Department of Gastroenterology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan; E-Mail:

关键词: Hepatitis C virus (HCV);    interferon (IFN)-lambda;    dendritic cells (DCs);    Toll-like receptor 3 (TLR3);    natural killer (NK) cell;    cytotoxic T lymphocyte (CTL);   

DOI  :  10.3390/s151027160

来源: mdpi

【 摘 要 】

Hepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse. Human hepatocytes barely express TLR3 under non-infectious states, but frequently express it in HCV infection. Type I and III IFNs are induced upon stimulation with polyI:C, an analog of double-stranded (ds)RNA. Activation of TLR3 and the TICAM-1 pathway, followed by DC-mediated activation of cellular immunity, is augmented during exposure to viral RNA. Although type III IFNs are released from replication-competent human hepatocytes, DC-mediated CTL proliferation and NK cell activation hardly occur in response to the released type III IFNs. Yet, type I IFNs and HCV-infected hepatocytes can induce maturation of DCs in either human or mouse origin. In addition, mouse CD8+ DCs mature in response to HCV-infected hepatocytes unless the TLR3/TICAM-1 pathway is blocked. We found the exosomes containing HCV RNA in the supernatant of the HCV-infected hepatocytes act as a source of TLR3-mediated DC maturation. Here we summarize our view on the mechanism by which DCs mature to induce NK and CTL in a status of HCV infection.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.