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Front. Immunol. | doi: 10.3389/fimmu.2018.02686

Regulating innate and adaptive immunity for controlling SIV infection by25-hydroxycholesterol

 Caijun Sun1, 2*,  Tongjin Wu1, 3,  Feng Ma4, Xiuchang Ma2, Weizhe Jia1,  Pan Enxiang2, Genhong Cheng5 and Ling Chen2
  • 1Sun Yat-sen University, China
  • 2Guangzhou Institutes of Biomedicine and Health (CAS), China
  • 3Anhui University, China
  • 4Center of Systems Medicine,Chinese Academy of Medical Sciences,Suzhou Institute of Systems Medicine, China
  • 5University of California, Los Angeles, United States

Persistent inflammation and extensive immune activation have been associated with HIV-1/SIV pathogenesis. Previously, we reported that cholesterol-25-hydroxylase (CH25H) and its metabolite 25-hydroxycholesterol (25-HC) had a broad antiviral activity in inhibiting Zika, Ebola, and HIV-1 infection. However, the underlying immunological mechanism of CH25H and 25-HC in inhibiting viral infection remains poorly understood. We report here that 25-HC effectively regulates immune responses for controlling viral infection. CH25H expression was interferon-dependent and induced by SIV infection in monkey-derived macrophages and PBMC cells, and 25-HC inhibited SIV infection both in permissive cell lines and primary monkey lymphocytes. 25-HC also strongly inhibited bacterial lipopolysaccharide (LPS)-stimulated inflammation and restricted mitogen-stimulated proliferation in primary monkey lymphocytes. Strikingly, 25-HC promoted SIV-specific IFN-γ-producing cellular responses, but selectively suppressed proinflammatory CD4+ T lymphocytes secreting IL-2 and TNF-α cytokines in vaccinated mice. In addition, 25-HC had no significant immunosuppressive effects on cytotoxic CD8+ T lymphocytes or antibody-producing B lymphocytes. Collectively, 25-HC modulated both innate and adaptive immune responses towards inhibiting HIV/SIV infection. This study provides insights into improving vaccination and immunotherapy regimes against HIV-1 infection.

Keywords: HIV – human immunodeficiency virus, inflamation, CTL (Cytotoxic T lymphocyte), Immunotherapy, 25-HC

Received: 23 Jul 2018; Accepted: 31 Oct 2018.

Edited by:

Rashika El Ridi, Cairo University, Egypt

Reviewed by:

David Lembo, Università degli Studi di Torino, Italy
Geoffrey Holm, Colgate University, United States  

Copyright: © 2018 Sun, Wu, Ma, Ma, Jia, Enxiang, Cheng and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Caijun Sun, Sun Yat-sen University, Guangzhou, China, suncaijun@mail.sysu.edu.cn