IPS-1 is essential for type III IFN production by Hepatocytes and Dendritic cells in response to Hepatitis C virus infection

Masaaki Okamoto, Hiroyuki Oshiumi, Masahiro Azuma, Nobuyuki Kato, Misako Matsumoto, Tsukasa Seya

Research output: Contribution to journalArticle

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Abstract

Hepatitis C virus (HCV) is a major cause of liver disease. The innate immune system is essential for controllingHCV replication, and HCV is recognized by RIG-I and TLR3, which evoke innate immune responses through IPS-1 and TICAM-1 adaptor molecules, respectively. IL-28B is a type III IFN, and genetic polymorphisms upstream of its gene are strongly associated with the efficacy of polyethylene glycol-IFN and ribavirin therapy. As seen with type I IFNs, type III IFNs induce antiviral responses to HCV. Recent studies established the essential role of TLR3-TICAM-1 pathway in type III IFN production in response to HCV infection. Contrary to previous studies, we revealed an essential role of IPS-1 in type III IFN production in response to HCV. First, using IPS-1 knockout mice, we revealed that IPS-1 was essential for type III IFN production by mouse hepatocytes and CD8+ dendritic cells (DCs) in response to cytoplasmic HCV RNA. Second, we demonstrated that type III IFN induced RIG-I but not TLR3 expression in CD8+ DCs and augmented type III IFN production in response to cytoplasmic HCV RNA. Moreover, we showed that type III IFN induced cytoplasmic antiviral protein expression in DCs and hepatocytes but failed to promote DC-mediated NK cell activation or cross-priming. Our study indicated that IPS-1-dependent pathway plays a crucial role in type III IFN production by CD8+ DCs and hepatocytes in response to HCV, leading to cytoplasmic antiviral protein expressions. The Journal of Immunology, 2014, 192: 2770-2777.

Original languageEnglish
Pages (from-to)2770-2777
Number of pages8
JournalJournal of Immunology
Volume192
Issue number6
DOIs
Publication statusPublished - Mar 15 2014

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Virus Diseases
Hepacivirus
Dendritic Cells
Hepatocytes
Antiviral Agents
Cross-Priming
RNA
Ribavirin
Genetic Polymorphisms
Allergy and Immunology
Innate Immunity
Knockout Mice
Natural Killer Cells
Liver Diseases
Immune System
Proteins
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

IPS-1 is essential for type III IFN production by Hepatocytes and Dendritic cells in response to Hepatitis C virus infection. / Okamoto, Masaaki; Oshiumi, Hiroyuki; Azuma, Masahiro; Kato, Nobuyuki; Matsumoto, Misako; Seya, Tsukasa.

In: Journal of Immunology, Vol. 192, No. 6, 15.03.2014, p. 2770-2777.

Research output: Contribution to journalArticle

Okamoto, Masaaki ; Oshiumi, Hiroyuki ; Azuma, Masahiro ; Kato, Nobuyuki ; Matsumoto, Misako ; Seya, Tsukasa. / IPS-1 is essential for type III IFN production by Hepatocytes and Dendritic cells in response to Hepatitis C virus infection. In: Journal of Immunology. 2014 ; Vol. 192, No. 6. pp. 2770-2777.
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