NLRC4 inflammasome-mediated production of IL-1β modulates mucosal immunity in the lung against gram-negative bacterial infection.
NLRC4 inflammasome-mediated production of IL-1β modulates mucosal immunity in the lung against gram-negative bacterial infection.
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DOI：
10.4049/jimmunol.1200195
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发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Jeyaseelan S
中科院分区：
文献类型：
--
作者：
Cai S;Batra S;Wakamatsu N;Pacher P;Jeyaseelan S
细菌鞭毛蛋白对介导NLRC 4炎性小体依赖性caspase-1活化至关重要。然而，已知福氏志贺菌（一种非鞭毛细菌）和铜绿假单胞菌（Pa）的鞭毛蛋白（fliC）敲除菌株激活骨髓来源的巨噬细胞中的NLRC 4。此外，在腹膜炎小鼠模型中使用Pa的fliC敲除菌株以显示NLRC 4的需要。在肺Pa感染的模型中，鞭毛蛋白被证明是诱导NLRC 4依赖性半胱天冬酶-1活化所必需的。此外，在所有Pa研究中，NLRC 4 −/−小鼠中IL-1β的产生减弱;然而，没有探索IL-1β在NLRC 4介导的肺部先天免疫中对非鞭毛细菌的作用。在这里，我们报告说，NLRC 4是重要的宿主生存和细菌清除，以及肺炎克雷伯氏菌（Kp）感染后肺部嗜中性粒细胞介导的炎症。NLRC 4对于肺中KP诱导的IL-1β、IL-17 A和中性粒细胞化学引诱物（KC、MIP-2和LIX）的产生至关重要。造血细胞中的NLRC 4信号传导有助于Kp诱导的肺部炎症。此外，外源性IL-1β，而不是IL-18或IL-17 A，部分挽救了感染性攻击后NLRC 4 −/−小鼠肺中的存活率、中性粒细胞蓄积和细胞因子/趋化因子表达。此外，IL-1 R1 −/−小鼠在感染后肺部的嗜酸性炎症减少。总之，这些发现提供了新的见解NLRC 4在KP诱导的宿主防御中的作用。
Bacterial flagellin is critical to mediate NLRC4 inflammasome-dependent caspase-1 activation. However, Shigella flexneri, a non-flagellated bacterium, and a flagellin (fliC) knockout strain of Pseudomonas aeruginosa (Pa) are known to activate NLRC4 in bone marrow-derived macrophages. Furthermore, the fliC knockout strain of Pa was used in a mouse model of peritonitis to show the requirement of NLRC4. In a model of pulmonary Pa infection, flagellin was shown to be essential for the induction of NLRC4-dependent caspase-1 activation. Moreover, in all Pa studies, IL-1β production was attenuated in NLRC4−/− mice; however, the role of IL-1β in NLRC4-mediated innate immunity in the lungs against a non-flagellated bacterium was not explored. Here, we report that NLRC4 is important for host survival and bacterial clearance as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae (Kp) infection. NLRC4 is essential for Kp-induced production of IL-1β, IL-17A, and neutrophil chemoattractants (KC, MIP-2, and LIX) in the lungs. NLRC4 signaling in hematopoietic cells contributes to Kp-induced lung inflammation. Furthermore, exogenous IL-1β, but not IL-18 or IL-17A, partially rescued survival, neutrophil accumulation and cytokine/chemokine expression in the lungs of NLRC4−/− mice following infectious challenge. Furthermore, IL-1R1−/− mice displayed a decrease in neutrophilic inflammation in the lungs after infection. Taken together, these findings provide novel insights into the role of NLRC4 in Kp-induced host defense.
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DOI：
10.4049/jimmunol.0903843
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cai S;Batra S;Lira SA;Kolls JK;Jeyaseelan S
通讯作者：
Jeyaseelan S
DOI：
10.1165/rcmb.2008-0152oc
发表时间：
2009-06-01
影响因子：
6.4
作者：
Cai, Shanshan;Zemans, Rachel L.;Jeyaseelan, Samithamby
通讯作者：
Jeyaseelan, Samithamby
DOI：
10.1046/j.1365-2370.2002.00266.x
发表时间：
2002-02-01
期刊：
EUROPEAN JOURNAL OF IMMUNOGENETICS
影响因子：
--
作者：
Balch, SG;Greaves, DR;McKnight, AJ
通讯作者：
McKnight, AJ
影响因子：
3.1
作者：
Balamayooran, Theivanthiran;Batra, Sanjay;Jeyaseelan, Samithamby
通讯作者：
Jeyaseelan, Samithamby
影响因子：
5.4
作者：
Franchi, Luigi;Stoolman, Joshua;Nunez, Gabriel
通讯作者：
Nunez, Gabriel