title: IFN-stimulated gene LY6E in monocytes regulates the CD14/TLR4 pathway but inadequately restrains the hyperactivation of monocytes during chronic HIV-1 infection.
abstract: Owing to ongoing recognition of pathogen-associated molecular patterns, immune activation and upregulation of IFN-stimulated genes (ISGs) are sustained in the chronically infected host. Albeit most ISGs are important effectors for containing viral replication, some might exert compensatory immune suppression to limit pathological dysfunctions, although the mechanisms are not fully understood. In this study, we report that the ISG lymphocyte Ag 6 complex, locus E (LY6E) is a negative immune regulator of monocytes. LY6E in monocytes negatively modulated CD14 expression and subsequently dampened the responsiveness to LPS stimulation in vitro. In the setting of chronic HIV infection, the upregulation of LY6E was correlated with reduced CD14 level on monocytes; however, the immunosuppressive effect of LY6E was not adequate to remedy the hyperresponsiveness of activated monocytes. Taken together, the regulatory LY6E pathway in monocytes represents one of negative feedback mechanisms that counterbalance monocyte activation, which might be caused by LPS translocation through the compromised gastrointestinal tract during persistent HIV-1 infection and may serve as a potential target for immune intervention.
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China; Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin 300071, China;
authors.forename: Xuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China; jianqingxu2008@gmail.com wentaoqiao@nankai.edu.cn qiuchao@fudan.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin 300071, China;
authors.forename: Lishuang
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Weihui
authors.initials: W
authors.lastname: Fu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Linxia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Yuncheng Center for Disease Control and Prevention, Shanxi 044400, China;
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Shanghai Center for Disease Control and Prevention, Shanghai 200336, China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin 300071, China;
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China; State Key Laboratory for Infectious Disease Prevention and Control, China Centers for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin 300071, China; jianqingxu2008@gmail.com wentaoqiao@nankai.edu.cn qiuchao@fudan.edu.cn.
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China; State Key Laboratory for Infectious Disease Prevention and Control, China Centers for Disease Control and Prevention, Beijing 102206, China jianqingxu2008@gmail.com wentaoqiao@nankai.edu.cn qiuchao@fudan.edu.cn.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D041981:Gastrointestinal Tract / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007108:Immune Tolerance; D050835:Interferon Regulatory Factors / Q000235:genetics; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D014779:Virus Replication / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D058851:GPI-Linked Proteins; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; C439870:LY6E protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha