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J Viral Hepat. 2013 Jun;20(6):385-94. doi: 10.1111/jvh.12040. Epub 2013 Jan 7.

Induction of interferon-λ contributes to Toll-like receptor-3-activated hepatic stellate cell-mediated hepatitis C virus inhibition in hepatocytes.

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1
The Center for Animal Experiment and ABSL-3 Laboratory, Wuhan University, Hubei, China.

Abstract

There is limited information about the role of hepatic stellate cells (HSC) in liver innate immunity against hepatitis C virus (HCV). We thus examined whether HSC can produce antiviral factors that inhibit HCV replication in human hepatocytes. HSC expressed functional Toll-like receptor 3 (TLR-3), which could be activated by its ligand, polyinosine-polycytidylic acid (poly I:C), leading to the induction of interferon-λ (IFN-λ) at both mRNA and protein levels. TLR-3 signalling of HSC also induced the expression of IFN regulatory factor 7 (IRF-7), a key regulator of IFN signalling pathway. When HCV JFH-1-infected Huh7 cells were co-cultured with HSC activated with poly I:C or incubated in media conditioned with supernatant (SN) from poly I:C-activated HSC, HCV replication was significantly suppressed. This HSC SN action on HCV inhibition was mediated through IFN-λ, which was evidenced by the observation that antibody to IFN-λ receptors could neutralize the HSC-mediated anti-HCV effect. The role of IFN-λ in HSC-mediated anti-HCV activity is further supported by the observation that HSC SN treatment induced the expression of IRF-7 and IFN-stimulated genes (ISGs), OAS-1 and MxA in HCV-infected Huh7 cells. These observations indicate that HSC may be a key regulatory bystander, participating in liver innate immunity against HCV infection using an IFN-λ-dependent mechanism.

PMID:
23647955
PMCID:
PMC3648885
DOI:
10.1111/jvh.12040
[Indexed for MEDLINE]
Free PMC Article
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