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HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes

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...

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Autores principales: Wang, Yizhong, Li, Jieliang, Wang, Xu, Zhou, Yu, Zhang, Ting, Ho, Wenzhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Kowsar 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546812/
https://www.ncbi.nlm.nih.gov/pubmed/26322111
http://dx.doi.org/10.5812/hepatmon.29282
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author Wang, Yizhong
Li, Jieliang
Wang, Xu
Zhou, Yu
Zhang, Ting
Ho, Wenzhe
author_facet Wang, Yizhong
Li, Jieliang
Wang, Xu
Zhou, Yu
Zhang, Ting
Ho, Wenzhe
author_sort Wang, Yizhong
collection PubMed
description 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.
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spelling pubmed-45468122015-08-30 HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes Wang, Yizhong Li, Jieliang Wang, Xu Zhou, Yu Zhang, Ting Ho, Wenzhe Hepat Mon Research Article 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. Kowsar 2015-08-30 /pmc/articles/PMC4546812/ /pubmed/26322111 http://dx.doi.org/10.5812/hepatmon.29282 Text en Copyright © 2015, Kowsar Corp. http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
spellingShingle Research Article
Wang, Yizhong
Li, Jieliang
Wang, Xu
Zhou, Yu
Zhang, Ting
Ho, Wenzhe
HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
title HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
title_full HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
title_fullStr HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
title_full_unstemmed HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
title_short HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
title_sort hcv dsrna-activated macrophages inhibit hcv replication in hepatocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546812/
https://www.ncbi.nlm.nih.gov/pubmed/26322111
http://dx.doi.org/10.5812/hepatmon.29282
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