中科院生物物理研究所:抗细菌天然免疫的新机制

Nature Immunology

1/1/18Article

21.506

影响因子

原标题:ER膜接头蛋白ERAdP感知细菌第二信使c-di-AMP和启动抗细菌免疫

① 环磷酸二腺苷(c-di-AMP)是由细菌分泌的第二信使,内质网接头蛋白ERAdP可作为c-di-AMP的直接传感器;② ERAdP缺陷小鼠对单增李斯特菌感染高度易感、促炎细胞因子的分泌减少;③ c-di-AMP结合ERAdP的C端结构域导致ERAdP二聚化,进而结合并活化激酶TAK1,后者启动转录因子NF-κB,以诱导促炎性细胞因子的产生;④ ERAdP和TAK1双敲除,小鼠对单增李斯特菌感染易感性更高;⑤ ERAdP介导生成促炎性细胞因子,对调控细菌感染有重要作用。

环磷酸二腺苷(c-di-AMP) 内质网接头蛋白ERAdP 抗细菌免疫 天然免疫细胞

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Title:
The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity

DOI:
10.1038/s41590-017-0014-x

Abstract & Authors展开

Abstract:
Cyclic diadenylate monophosphate (c-di-AMP) is secreted by bacteria as a secondary messenger. How immune cells detect c-di-AMP and initiate anti-bacterial immunity remains unknown. We found that the endoplasmic reticulum (ER) membrane adaptor ERAdP acts as a direct sensor for c-di-AMP. ERAdP-deficient mice were highly susceptible to Listeria monocytogenes infection and exhibited reduced pro-inflammatory cytokines. Mechanistically, c-di-AMP bound to the C-terminal domain of ERAdP, which in turn led to dimerization of ERAdP, resulting in association with and activation of the kinase TAK1. TAK1 activation consequently initiated activation of the transcription factor NF-κB to induce the production of pro-inflammatory cytokines in innate immune cells. Moreover, double-knockout of ERAdP and TAK1 resulted in heightened susceptibility to L. monocytogenes infection. Thus, ERAdP-mediated production of pro-inflammatory cytokines is critical for controlling bacterial infection.

All Authors:
Pengyan Xia,Shuo Wang,Zhen Xiong,Xiaoxiao Zhu,Buqing Ye,Ying Du,Shu Meng,Yuan Qu,Jing Liu,Guangxia Gao,Yong Tian,Zusen Fan

First Authors:
Pengyan Xia,Shuo Wang,Zhen Xiong,Xiaoxiao Zhu

Correspondence:
Yong Tian,Zusen Fan

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