NLRC4 expression in intestinal epithelial cells mediates protection against an enteric pathogen.
NLRC4 expression in intestinal epithelial cells mediates protection against an enteric pathogen.
复制标题
NLRC4在肠上皮细胞中的表达介导了针对肠道病原体的保护。
作者：
炎性小体在将内源性和微生物危险信号的检测与半胱天冬酶-1活化和诱导保护性免疫应答相联系方面发挥重要作用。NLRC 4是一种胞质NOD样受体（NLR），其可以响应于细菌鞭毛蛋白（肠道中的免疫显性抗原）而触发炎性小体形成。为了表征NLRC 4在细菌引发的肠道炎症中的作用，我们使用了鼠病原体啮齿柠檬酸杆菌，一种与EHEC和EPEC相似的细胞外附着/消失细菌。感染C.在啮齿动物中，我们发现Nlrc 4 −/−小鼠与WT小鼠相比体重减轻更严重，细菌定植水平增加，肠道炎症加剧。Nlrc 4 −/−小鼠产生了强大的适应性免疫应答，但无法控制C.啮齿类动物，表明先天免疫缺陷负责。使用骨髓嵌合体的实验显示，NLRC 4的保护作用依赖于其在非造血细胞中的表达，定量PCR分析显示，NLRC 4在上皮隐窝中高度表达，但在肠基质中不表达。因此，肠上皮细胞中的早期NLRC 4传感调节细胞外细菌病原体的定植并限制随后的肠损伤。
The inflammasomes play an important role in connecting the detection of endogenous and microbial danger signals to caspase-1 activation and induction of protective immune responses. NLRC4 is a cytosolic NOD-like receptor (NLR) that can trigger inflammasome formation in response to bacterial flagellin, an immunodominant antigen in the intestine. To characterize the role of NLRC4 in bacterially-triggered intestinal inflammation, we used the murine pathogen Citrobacter rodentium, an extracellular, attaching/effacing bacterium similar to EHEC and EPEC. Following infection with C. rodentium, we found that Nlrc4−/− mice developed more severe weight loss, increased bacterial colonization levels and exacerbated intestinal inflammation compared to WT counterparts. Nlrc4−/− mice mounted robust adaptive immune responses, but were unable to control early colonization by C. rodentium, suggesting that a defect in innate immunity was responsible. Experiments using bone marrow chimeras revealed that the protective effects of NLRC4 were dependent on its expression in non-hematopoietic cells and quantitative PCR analyses revealed that NLRC4 was highly expressed in epithelial crypts but not in intestinal stroma. Thus, early NLRC4 sensing in intestinal epithelial cells regulates colonization by an extracellular bacterial pathogen and limits subsequent intestinal damage.
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影响因子：
29.4
作者：
Asquith MJ;Boulard O;Powrie F;Maloy KJ
通讯作者：
Maloy KJ
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：
30.5
作者：
Franchi, Luigi;Amer, Amal;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
29.4
作者：
Darfeuille-Michaud, A;Neut, C;Colombel, JF
通讯作者：
Colombel, JF
影响因子：
30.5
作者：
通讯作者：
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