title: Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.
abstract: Type I interferon (IFN) production plays pivotal roles in host antiviral innate immune responses, but an excessive production of type I IFN leads to the development of immunopathological conditions. Investigations on the regulatory mechanisms underlying host type I IFN production are currently of great interest. Here, we found that the expression of lectin family member Siglec1 was upregulated by viral infection in macrophages, which was dependent on the IFN/JAK/STAT1 signaling pathway. Siglec1 was found to negatively regulate viral infection-triggered type I IFN production. Mechanistically, Siglec1 associates with DAP12 to recruit and activate the scaffolding function of SHP2; SHP2 then recruits E3 ubiquitin ligase TRIM27, which induces TBK1 degradation via K48-linked ubiquitination at Lys251 and Lys372. Therefore, viral infection-induced upregulation of Siglec1 feedback loop inhibits type I IFN production and suppresses antiviral innate immune responses. Our study outlines a novel mechanism of negative regulation of type I IFN production, which may help virus to escape immune elimination.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Yingyun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xie
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.|National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.|National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D059748:Proteolysis; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000276:immunology*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism; D000070584:Tripartite Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D063267:Sialic Acid Binding Ig-like Lectin 1; D044767:Ubiquitin-Protein Ligases; C494233:Irf3 protein, mouse; C571167:Siglec1 protein, mouse; C489296:Trim27 protein, mouse; D000070584:Tripartite Motif Proteins; C498588:Tbk1 protein, mouse