NAIP-NLRC4-deficient mice are susceptible to shigellosis.
NAIP-NLRC4-deficient mice are susceptible to shigellosis.
复制标题
DOI：
10.7554/elife.59022
复制
发表时间：
2020-10-19
期刊：
影响因子：
7.7
通讯作者：
Vance RE
中科院分区：
文献类型：
--
作者：
Mitchell PS;Roncaioli JL;Turcotte EA;Goers L;Chavez RA;Lee AY;Lesser CF;Rauch I;Vance RE
志贺氏菌属的细菌引起志贺氏菌病，这是一种严重的胃肠道疾病，是人类中与志贺氏菌相关的死亡的主要原因。小鼠对志贺氏菌具有高度抗性，并且缺乏易处理的志贺氏菌病生理模型阻碍了我们对这种重要的人类疾病的理解。在这里，我们提出小鼠和人类对志贺氏菌的不同易感性是由于NAIP-NLRC 4炎性体的小鼠特异性激活。我们发现NAIP-NLRC 4缺陷小鼠对口服志贺氏菌感染高度敏感，并概括了人类志贺氏菌病的临床特征。虽然炎性小体通常被认为促进志贺氏菌的发病机制，但我们证明肠上皮细胞（IEC）特异性NAIP-NLRC 4活性足以保护小鼠免受志贺氏菌感染。除了描述一种新的小鼠志贺氏菌病模型外，我们的研究结果表明，IEC中缺乏炎性小体反应可能有助于解释人类对志贺氏菌病的易感性。
Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease that is a major cause of diarrhea-associated mortality in humans. Mice are highly resistant to Shigella and the lack of a tractable physiological model of shigellosis has impeded our understanding of this important human disease. Here, we propose that the differential susceptibility of mice and humans to Shigella is due to mouse-specific activation of the NAIP–NLRC4 inflammasome. We find that NAIP–NLRC4-deficient mice are highly susceptible to oral Shigella infection and recapitulate the clinical features of human shigellosis. Although inflammasomes are generally thought to promote Shigella pathogenesis, we instead demonstrate that intestinal epithelial cell (IEC)-specific NAIP–NLRC4 activity is sufficient to protect mice from shigellosis. In addition to describing a new mouse model of shigellosis, our results suggest that the lack of an inflammasome response in IECs may help explain the susceptibility of humans to shigellosis.