Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative Pseudomonas aeruginosa.
Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative Pseudomonas aeruginosa.
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DOI：
10.1038/s41420-018-0068-z
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发表时间：
2018
影响因子：
7
通讯作者：
Kanneganti TD
中科院分区：
文献类型：
--
作者：
Balakrishnan A;Karki R;Berwin B;Yamamoto M;Kanneganti TD
细菌配体的检测是激活炎症体的先决条件。在铜绿假单胞菌感染过程中，通过T3SS分泌的鞭毛蛋白被NLRC4炎症体检测到。在慢性铜绿假单胞菌感染的囊性纤维化患者中，NLRC4炎症小体的激活被认为是导致高IL-1β产生和致病性的原因。有趣的是，从囊性纤维化合并慢性呼吸道感染的患者中分离出的大多数铜绿假单胞菌是非运动性的，T3SS阴性，这表明尚未确定的炎症小体途径调节囊性纤维化患者IL-1β的产生。在这里，我们展示了鸟苷结合蛋白(GBP)在调节细菌增殖和炎性小体激活方面的作用，以响应T3SS阴性的铜绿假单胞菌。通过GbP2和IRGB10作用释放的细菌配体激活Caspase-11，调节非典型的NLRP3炎症小体激活和IL-1β的释放。总之，我们的结果揭示了caspase-11在T3SS阴性铜绿假单胞菌感染过程中抑制细菌增殖和促进IL-1β分泌的作用。这项研究表明，非规范炎症体可能已经共同进化来检测革兰氏阴性细菌病原体，这些细菌已经进化成绕过规范NLR的检测。
Detection of bacterial ligands is a pre-requisite for inflammasome activation. During Pseudomonas aeruginosa infection, flagellin which is secreted through the T3SS is detected by the NLRC4 inflammasome. Activation of the NLRC4 inflammasome is believed to contribute to high IL-1β production and pathogenicity in cystic fibrosis patients with chronic P. aeruginosa infection. Interestingly, the majority of P. aeruginosa isolated from cystic fibrosis patients with chronic airway infection are non-motile and T3SS-negative, suggesting that yet un-characterized inflammasome pathways regulate IL-1β production in cystic fibrosis patients. Here we demonstrate the role of guanylate-binding proteins (GBPs) in regulating bacterial proliferation and inflammasome activation in response to T3SS-negative P. aeruginosa. Bacterial ligands liberated by the action of GBP2 and IRGB10 activate caspase-11 and regulate non-canonical NLRP3 inflammasome activation and IL-1β release. Overall, our results reveal the role of caspase-11 in inhibiting bacterial proliferation and promoting IL-1β secretion during T3SS-negative P. aeruginosa infection. This study suggests that non canonical inflammasomes might have co-evolved to detect Gram-negative bacterial pathogens that have evolved to bypass detection by canonical NLRs.
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影响因子：
56.9
作者：
Kim, Bae-Hoon;Shenoy, Avinash R.;MacMicking, John D.
通讯作者：
MacMicking, John D.
影响因子：
5.4
作者：
Franchi, Luigi;Stoolman, Joshua;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
16.6
作者：
Rimessi, Alessandro;Bezzerri, Valentino;Pinton, Paolo
通讯作者：
Pinton, Paolo
DOI：
10.1084/jem.20132234
发表时间：
2016-05-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Qu Y;Misaghi S;Newton K;Maltzman A;Izrael-Tomasevic A;Arnott D;Dixit VM
通讯作者：
Dixit VM
影响因子：
3.1
作者：
MAHENTHIRALINGAM, E;CAMPBELL, ME;SPEERT, DP
通讯作者：
SPEERT, DP