The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response

被引：339

作者：

Parvatiyar, Kislay ^{[1
]}

Zhang, Zhiqiang ^{[2
]}

Teles, Rosane M. ^{[3
]}

Ouyang, Songying ^{[4
]}

Jiang, Yan ^{[4
]}

Iyer, Shankar S. ^{[1
]}

Zaver, Shivam A. ^{[1
]}

Schenk, Mirjam ^{[3
]}

Zeng, Shang ^{[5
]}

Zhong, Wenwan ^{[5
]}

Liu, Zhi-Jie ^{[4
]}

Modlin, Robert L. ^{[1
,3
]}

Liu, Yong-jun ^{[2
]}

Cheng, Genhong ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[2] Baylor Res Inst, Baylor Inst Immunol Res, Dallas, TX USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA

[4] Chinese Acad Sci, Inst Biophys, Beijing 100080, Peoples R China

[5] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 12期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

INNATE; RECEPTORS; ADAPTER; FACTOR-3; REVEALS; SENSOR;

D O I：

10.1038/ni.2460

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The induction of type I interferons by the bacterial secondary messengers cyclic di-GMP (c-di-GMP) or cyclic di-AMP (c-di-AMP) is dependent on a signaling axis that involves the adaptor STING, the kinase TBK1 and the transcription factor IRF3. Here we identified the heliase DDX41 as a pattern-recognition receptor (PRR) that sensed both c-di-GMP and c-di-AMP. DDX41 specifically and directly interacted with c-di-GMP. Knockdown of DDX41 via short hairpin RNA in mouse or human cells inhibited the induction of genes encoding molecules involved in the innate immune response and resulted in defective activation of STING, TBK1 and IRF3 in response to c-di-GMP or c-di-AMP. Our results suggest a mechanism whereby c-di-GMP and c-di-AMP are detected by DDX41, which forms a complex with STING to signal to TBK1-IRF3 and activate the interferon response.

引用

页码：1155 / +

页数：8

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