Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen.
Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen.
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作者：
细胞内模式识别受体基因NLRP3的多态性与克罗恩病(一种炎症性肠病)的易感性有关。在组织损伤或感染后，NLRP3触发含有NLRP3、Asc和Caspase-1的炎症小体的形成，这些炎症小体介导IL-1β和IL-18的分泌。然而，NLRP3炎性小体在粘膜炎症和屏障保护中的确切作用仍不清楚。在这里，我们发现，当感染附着/消失(A/E)肠道病原体轮状柠檬酸杆菌时，Nlrp3−/−和Asc−/−小鼠表现出更多的细菌定植和分散，更严重的体重减轻和加重的肠道炎症。对辐射骨髓嵌合体的分析表明，对疾病的保护是通过激活非造血细胞中的Nlrp3来实现的，并且在感染后很早就开始了。因此，肠上皮细胞中Nlrp3的早期激活限制了病原体的定植，并防止了随后的病理，潜在地提供了NLRP3基因多态与IBD易感性之间的功能联系。
Polymorphisms in the intracellular pattern recognition receptor gene NLRP3 have been associated with susceptibility to Crohn’s disease, a type of inflammatory bowel disease (IBD). Following tissue damage or infection, NLRP3 triggers the formation of inflammasomes, containing NLRP3, ASC and caspase-1, which mediate secretion of IL-1β and IL-18. However, the precise role of NLRP3 inflammasomes in mucosal inflammation and barrier protection remains unclear. Here we show that upon infection with the attaching/effacing (A/E) intestinal pathogen Citrobacter rodentium, Nlrp3−/− and Asc−/− mice displayed increased bacterial colonization and dispersion, more severe weight loss and exacerbated intestinal inflammation. Analyses of irradiation bone marrow chimeras revealed that protection from disease was mediated through Nlrp3 activation in non-hematopoietic cells and was initiated very early after infection. Thus, early activation of Nlrp3 in intestinal epithelial cells limits pathogen colonization and prevents subsequent pathology, potentially providing a functional link between NLRP3 polymorphisms and susceptibility to IBD.
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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
4.8
作者：
Liu, Zhiping;Zaki, Md Hasan;Kanneganti, Thirumala-Devi
通讯作者：
Kanneganti, Thirumala-Devi
影响因子：
24.5
作者：
Bauer, Christian;Duewell, Peter;Schnurr, Max
通讯作者：
Schnurr, Max
DOI：
10.1084/jem.20100050
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen IC;TeKippe EM;Woodford RM;Uronis JM;Holl EK;Rogers AB;Herfarth HH;Jobin C;Ting JP
通讯作者：
Ting JP
影响因子：
32.4
作者：
Kim YG;Kamada N;Shaw MH;Warner N;Chen GY;Franchi L;Núñez G
通讯作者：
Núñez G