HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
| Author | Yizhong Wang | en |
| Author | Jieliang Li | en |
| Author | Xu Wang | en |
| Author | Yu Zhou | en |
| Author | Ting Zhang | en |
| Author | Wenzhe Ho | en |
| Issued Date | 2015-08-01 | en |
| Abstract | Background: Macrophages play critical roles in innate immune response in the liver. Whether macrophages participate in liver innate immunity against HCV replication is poorly understood Objectives: The aim of this study was to investigate the role of macrophages in liver innate immunity against HCV replication. Materials and Methods: Freshly isolated monocytes were purified from peripheral blood of healthy adult donors. Macrophages refer to 7-day-cultured monocytes in vitro. A hepatoma cell line (Huh7) was infected with HCV JFH-1 to generate in vitro HCV infectious system. RT-PCR was used to determine HCV RNA and mRNA levels of genes expression. ELISA was used to measure the protein level of interferon-α (IFN-α) and western blot was used to determine protein expression level of Toll-like receptor 3 (TLR3). Results: HCV dsRNA induced the expression of type I IFN (IFN-α/β) in monocyte-derived macrophages. HCV dsRNA also induced the expression of TLR3 and IFN regulatory factor-7 (IRF-7), the key regulators of the IFN signaling pathway. When HCV JFH-1-infected Huh7 cells were co-cultured with macrophages activated with HCV dsRNA or incubated in media conditioned with supernatant (SN) from HCV dsRNA-activated macrophages, HCV replication was significantly suppressed. This macrophage SN action on HCV inhibition was mediated through type I IFN, which was evidenced by the observation that antibody to type I IFN receptor could neutralize the macrophages-mediated anti-HCV effect. The role of type I IFN in macrophages-mediated anti-HCV activity is further supported by the observation that HCV dsRNA-activated macrophages SN treatment induced the expression of several IFN-stimulated genes (ISGs), ISG15, ISG56, OAS-1, OAS-2, MxA and Viperin in HCV-infected Huh7 cells. Conclusions: Macrophages may play an important role in liver innate immunity against HCV replication through a type I IFN-dependent mechanism. | en |
| DOI | https://doi.org/10.5812/hepatmon.29282 | en |
| Keyword | Hepatitis C Virus | en |
| Keyword | Interferon | en |
| Keyword | Macrophages | en |
| Keyword | Toll-Like Receptor 3 | en |
| Publisher | Brieflands | en |
| Title | HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes | en |
| Type | Research Article | en |
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