title: Hepatitis C virus regulates the production of monocytic myeloid-derived suppressor cells from peripheral blood mononuclear cells through PI3K pathway and autocrine signaling.
abstract: Hepatitis C virus (HCV) infection is a major liver disease that ultimately develops into chronic hepatitis. Consequently, such patients are predisposed to serious complications, such as hepatocellular carcinoma. In HCV-infected patients, impaired T-cell responses are associated with persistent infection. Myeloid-derived suppressor cells (MDSCs) play a pivotal role in suppressing T-cell responses. In this study, we investigated the capacity and mechanism through which HCV transforms CD14+ monocytes into monocytic (Mo)-MDSCs. We showed that HCV core protein promotes CD14+ monocytes to develop a CD14+HLA-DR/low phenotype with upregulated indoleamine 2,3-dioxygenase (IDO) expression and suppressed T-cell proliferation. Importantly, HCV-induced Mo-MDSC production was attributed to the PI3K pathway via induction of IL-10 and TNF-α secretion. This process could be reversed by polyinosinic:polycytidylic acid (polyI:C) treatment. In conclusion, our results suggest that HCV regulates Mo-MDSC production from monocytes through the PI3K pathway and autocrine cytokines. The latter can serve as effective targets for novel HCV therapies.
authors.affiliation: Department of Pediatric Gastroenterology, the First Hospital, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Pang
authors.affiliation: Translational Medicine Research Institute, the First Hospital, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Hongxiao
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Hepatology, the First Hospital, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Institute, the First Hospital, Jilin University, Changchun 130021, Jilin, China. Electronic address: zhengkuntu2013@126.com.
authors.forename: Zhengkun
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Hepatology, the First Hospital, Jilin University, Changchun 130021, Jilin, China. Electronic address: junqiniu2013@126.com.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
mesh_terms: D019898:Autocrine Communication; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D016174:Hepacivirus; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014758:Viral Core Proteins / Q000494:pharmacology
chemical_list: D016207:Cytokines; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D019869:Phosphatidylinositol 3-Kinases; D011070:Poly I-C
keywords: Autocrine cytokine; Hepatitis C virus; Monocytic myeloid-derived suppressor cell; PI3K pathway; Peripheral blood mononuclear cell