HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway
Adult
CD4-Positive T-Lymphocytes
Male
0301 basic medicine
Tumor Necrosis Factor-alpha
Macrophages
Viral Core Proteins
Nitric Oxide Synthase Type II
Cell Differentiation
Hepacivirus
Middle Aged
Antiviral Agents
Hepatitis C
Article
Monocytes
Toll-Like Receptor 2
3. Good health
03 medical and health sciences
Case-Control Studies
Humans
Female
Cells, Cultured
Signal Transduction
DOI:
10.1038/srep36160
Publication Date:
2016-10-27T10:32:24Z
AUTHORS (13)
ABSTRACT
AbstractHepatitis C virus (HCV) establishes persistent infection in most infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Monocytes and macrophages provide the first line of defense against pathogens, but their roles in HCV infection remains unclear. We have reported that HCV core protein (HCVc) manipulates human blood-derived dendritic cell development. In the present study, we tested whether HCVc affects human blood-derived monocyte differentiating into macrophages. Results showed that HCVc inhibits monocyte differentiation to either M1 or M2 macrophages through TLR2, associated with impaired STATs signaling pathway. Moreover, HCVc inhibits phagocytosis activity of M1 and M2 macrophages, M1 macrophage-induced autologous and allogeneic CD4+ T cell activation, but promotes M2 macrophage-induced autologous and allogeneic CD4+ T cell activation. In conclusion, HCVc inhibits monocyte-derived macrophage polarization via TLR2 signaling, leading to dysfunctions of both M1 and M2 macrophages in chronic HCV infected patients. This may contribute to the mechanism of HCV persistent infection, and suggest that blockade of HCVc might be a novel therapeutic approach to treating HCV infection.
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