Hepatitis C virus regulates the production of monocytic myeloid-derived suppressor cells from peripheral blood mononuclear cells through PI3K pathway and autocrine signaling

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Xiaoli PangJunqi Niu

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.

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Citations

Jan 5, 2017·Viral Immunology·Megan A O'ConnorWilliam R Green
Sep 25, 2018·Clinical and Experimental Immunology·D RiemannB Seliger
May 18, 2020·American Journal of Reproductive Immunology : AJRI·Zi-Meng ZhengJun Shao
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