nature-immunology201212-1

通过第二信使环鸟苷二磷酸和环腺苷二磷酸介导I型干扰素的激活依赖适配体蛋白STING。来自美国加州大学洛杉矶分校的Cheng及其同事发现解旋酶DDX41能够识别细菌内的这些第二信使,然后再与STING蛋白互作,进而将信号传递给TBK1-IRF3,从而激活干扰素响应。相关的研究论文于11月11日在线发表在《Nature Immunology》期刊上。

-2012年12月《自然-免疫》

中文翻译


【题目】解旋酶DDX41激活I型干扰素免疫响应

【译文】细菌第二信使环鸟苷二磷酸(c-di-GMP)或环腺苷二磷酸(c-di-AMP)依赖一信号途径,诱导细胞分泌I性干扰素,这一信号途径包括适配体蛋白STING、TBK1激酶和转录因子IRF3。本研究鉴定到解旋酶DDX41可作为模式识别受体(PRR),用于结合环鸟苷二磷酸和环腺苷二磷酸。DDX41特异性地直接与环鸟苷二磷酸结合。我们通过短发夹RNA沉默小鼠或人类细胞的DDX41,结果导致参与先天性免疫响应的基因诱导表达受抑制,且响应环鸟苷二磷酸或环腺苷二磷酸的STING、TBK1和IRF3不能被激活。本研究提出一个机制:DDX41能够识别第二信使鸟苷二磷酸和环腺苷二磷酸,然后与STING蛋白互作形成复合物,再将信号传递给TBK1-IRF3,从而激活干扰素响应。

英文原稿


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

[Authors]:: Kislay Parvatiyar, Zhiqiang Zhang, Rosane M Teles, Songying Ouyang, Yan Jiang, Shankar S Iyer, Shivam A Zaver, Mirjam Schenk, Shang Zeng, Wenwan Zhong, Zhi-Jie Liu, Robert L Modlin, Yong-jun Liu & Genhong Cheng

[Abstract]: 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 helicase 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.

原文地址

http://www.nature.com/ni/journal/v13/n12/abs/ni.2460.html

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