title: HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway.
abstract: Hepatitis 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.
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.|Department of Hepatobiliary and Pancreatic Diseases, the First Hospital of Jilin University, Changchun, China.|College of Clinical Medicine, Jining Medical University, Jining, China.
authors: Qianqian
authors: Q
authors: Zhang
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.
authors: Yang
authors: Y
authors: Wang
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.
authors: Naicui
authors: N
authors: Zhai
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.
authors: Hongxiao
authors: H
authors: Song
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.
authors: Haijun
authors: H
authors: Li
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.
authors: Yang
authors: Y
authors: Yang
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.
authors: Tianyang
authors: T
authors: Li
authors: Department of Hepatobiliary and Pancreatic Diseases, the First Hospital of Jilin University, Changchun, China.
authors: Xiaolin
authors: X
authors: Guo
authors: Department of Hepatobiliary and Pancreatic Diseases, the First Hospital of Jilin University, Changchun, China.
authors: Baorong
authors: B
authors: Chi
authors: Department of Hepatobiliary and Pancreatic Diseases, the First Hospital of Jilin University, Changchun, China.
authors: Junqi
authors: J
authors: Niu
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.|Department of Pathology, University of Washington, Seattle, WA, USA.
authors: Ian Nicholas
authors: IN
authors: Crispe
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.|Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Lishan
authors: L
authors: Su
authors: Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, China.|Department of Hepatobiliary and Pancreatic Diseases, the First Hospital of Jilin University, Changchun, China.
authors: Zhengkun
authors: Z
authors: Tu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D052247:Nitric Oxide Synthase Type II