Toll-like receptor 3-activated macrophages confer anti-HCV activity to hepatocytes through exosomes.
Exosomes are a class of cell-released small vesicles that mediate intercellular communication by delivering functional factors to recipient cells. During hepatitis C virus (HCV) infection, the interaction between liver resident macrophages and hepatocytes is a key component in liver innate immunity. In this study, we explored the role of exosomes in the delivery of innate anti-HCV factors to hepatocytes from macrophages. We showed that supernatant from TLR3-activated macrophage cultures could efficiently inhibit HCV replication in Huh7 cells. This macrophage-mediated anti-HCV activity was through exosomes because inhibiting exosomes could abrogate the action of macrophages. Further analyses demonstrated that TLR3-activated macrophages release exosomes that contain anti-HCV microRNA (miRNA)-29 family members. Inhibiting miRNA29 could restore HCV replication. These findings suggest a novel antiviral mechanism in liver innate immunity against HCV infection and provide insights to support further studies on developing exosome-based delivery system for disease treatment.-Zhou, Y., Wang, X., Sun, L., Zhou, L., Ma, T.-C., Song, L., Wu, J.-G., Li, J.-L., Ho, W.-Z. Toll-like receptor 3-activated macrophages confer anti-HCV activity to hepatocytes through exosomes.
Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA; and yu.zhou@temple.edu.
Yu
Y
Zhou
Xu
X
Wang
The State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Li
L
Sun
The State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Li
L
Zhou
The State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Tong-Cui
TC
Ma
Li
L
Song
The State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Jian-Guo
JG
Wu
The State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Jie-Liang
JL
Li
Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA; and wenzheho@temple.edu.|The State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Wen-Zhe
WZ
Ho
D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism / Q000821:virology*; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008099:Liver / Q000821:virology; D008264:Macrophages / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology
C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
exosomes; hepatitis C virus; miRNA