当前位置:  首页 >> 最新重要论文

最新重要论文

The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity, Nat Immunol, 19(2):141-150,1 Jan 2018

发布时间:2018年01月02日

Nature Immunology, 19(2):141-150,1 Jan 2018,DOI: 10.1038/s41590-017-0014-x

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

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

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.

文章链接:https://www.nature.com/articles/s41590-017-0014-x

 

 

    附件下载: