Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.
Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.
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Siglec1 通过泛素连接酶 TRIM27 诱导 TBK1 降解，从而抑制抗病毒先天免疫反应。
DOI：
10.1038/cr.2015.108
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发表时间：
2015
期刊：
影响因子：
44.1
通讯作者：
Cao Xuetao
中科院分区：
文献类型：
--
作者：
Zheng Qingliang;Hou Jin;Zhou Ye;Yang Yingyun;Xie Bing;Cao Xuetao
I型干扰素（IFN）的产生在宿主抗病毒天然免疫应答中起关键作用，但I型IFN的过量产生导致免疫病理学状况的发展。研究宿主I型干扰素产生的调控机制是目前研究的热点。在这里，我们发现，凝集素家族成员Siglec 1的表达上调病毒感染巨噬细胞，这是依赖于IFN/JAK/STAT 1信号通路。发现Siglec 1负调节病毒感染触发的I型IFN产生。在机制上，Siglec 1与DAP 12结合以募集和激活SHP 2的支架功能;然后SHP 2募集E3泛素连接酶TRIM 27，其通过K48连接的Lys 251和Lys 372处的泛素化诱导TBK 1降解。因此，病毒感染诱导的Siglec 1反馈环的上调抑制I型IFN的产生并抑制抗病毒先天免疫应答。我们的研究概述了一种新的机制，负调节I型IFN的生产，这可能有助于病毒逃避免疫清除。
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.