IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes

被引：297

作者：

Almine, Jessica F. ^{[1
,2
]}

O'Hare, Craig A. J. ^{[1
,2
]}

Dunphy, Gillian ^{[1
,2
]}

Haga, Ismar R. ^{[3
]}

Naik, Rangeetha J. ^{[1
]}

Atrih, Abdelmadjid ^{[4
]}

Connolly, Dympna J. ^{[5
]}

Taylor, Jordan ^{[1
]}

Kelsall, Ian R. ^{[1
]}

Bowie, Andrew G. ^{[5
]}

Beard, Philippa M. ^{[3
,6
,7
]}

Unterholzner, Leonie ^{[1
,2
]}

机构：

[1] Univ Dundee, Sch Life Sci, Div Cell Signalling & Immunol, Dundee DD1 5EH, Scotland

[2] Univ Lancaster, Div Biomed & Life Sci, Fac Hlth & Med, Lancaster LA1 4YQ, England

[3] Pirbright Inst, Pirbright GU24 0NF, Surrey, England

[4] Univ Dundee, Sch Life Sci, Fingerprints Prote Facil, Dundee DD1 5EH, Scotland

[5] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland

[6] Univ Edinburgh, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland

[7] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH25 9RG, Midlothian, Scotland

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 美国国家卫生研究院; 英国惠康基金; 爱尔兰科学基金会;

关键词：

INNATE IMMUNE SENSOR; CYCLIC GMP-AMP; INTRACELLULAR DNA; INTERFERON RESPONSE; CYTOSOLIC DNA; VIRUS-INFECTION; PROTEIN; ADAPTER; DEGRADATION; PATHWAY;

D O I：

10.1038/ncomms14392

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-g inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses. IFI16 is also required for the cGAMP-induced activation of STING, and interacts with STING to promote STING phosphorylation and translocation. We propose that the two DNA sensors IFI16 and cGAS cooperate to prevent the spurious activation of the type I interferon response.

引用

页数：15

共 53 条

[1]

cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING [J].