当前位置: X-MOL 学术PLOS Pathog. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection.
PLoS Pathogens ( IF 6.7 ) Pub Date : 2020-03-18 , DOI: 10.1371/journal.ppat.1008335
Wenbiao Wang 1 , Dingwen Hu 2 , Caifeng Wu 1 , Yuqian Feng 1 , Aixin Li 2 , Weiyong Liu 2 , Yingchong Wang 2 , Keli Chen 2 , Mingfu Tian 2 , Feng Xiao 2 , Qi Zhang 2 , Muhammad Adnan Shereen 2 , Weijie Chen 1 , Pan Pan 1 , Pin Wan 1 , Kailang Wu 2 , Jianguo Wu 1, 2
Affiliation  

One of the fundamental reactions of the innate immune responses to pathogen infection is the release of pro-inflammatory cytokines, including IL-1β, processed by the NLRP3 inflammasome. The stimulator of interferon genes (STING) has the essential roles in innate immune response against pathogen infections. Here we reveal a distinct mechanism by which STING regulates the NLRP3 inflammasome activation, IL-1β secretion, and inflammatory responses in human cell lines, mice primary cells, and mice. Interestingly, upon HSV-1 infection and cytosolic DNA stimulation, STING binds to NLRP3 and promotes the inflammasome activation through two approaches. First, STING recruits NLRP3 and facilitates NLRP3 localization in the endoplasmic reticulum, thereby facilitating the inflammasome formation. Second, STING interacts with NLRP3 and attenuates K48- and K63-linked polyubiquitination of NLRP3, thereby promoting the inflammasome activation. Collectively, we demonstrate that the cGAS-STING-NLRP3 signaling is essential for host defense against HSV-1 infection.



中文翻译:

STING促进ER中的NLRP3定位,并促进HSRP-1感染后NLRP3的去泛素化以激活炎性体。

先天性免疫应答对病原体感染的基本反应之一是由NLRP3炎性小体处理的促炎性细胞因子(包括IL-1β)的释放。干扰素基因的刺激物(STING)在针对病原体感染的天然免疫反应中起着至关重要的作用。在这里,我们揭示了STING调节人细胞系,小鼠原代细胞和小鼠中NLRP3炎症小体激活,IL-1β分泌和炎症反应的独特机制。有趣的是,在HSV-1感染和细胞质DNA刺激后,STING通过两种方法与NLRP3结合并促进炎性体激活。首先,STING募集NLRP3并促进NLRP3在内质网中的定位,从而促进炎性体的形成。第二,STING与NLRP3相互作用并减弱NLRP3的K48和K63连接的多泛素化作用,从而促进炎症小体的活化。总的来说,我们证明了cGAS-STING-NLRP3信号对于宿主防御HSV-1感染至关重要。

更新日期:2020-03-19
down
wechat
bug