CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT.
CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT.
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DOI：
10.1038/s41467-022-28967-5
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发表时间：
2022-03-11
影响因子：
16.6
通讯作者：
Shafikhani SH
中科院分区：
文献类型：
--
作者：
Mohamed MF;Gupta K;Goldufsky JW;Roy R;Callaghan LT;Wetzel DM;Kuzel TM;Reiser J;Shafikhani SH
3型分泌系统（T3SS）是一个高度保守的毒力结构，在包括铜绿假单胞菌在内的许多革兰氏阴性致病菌的发病机制中起重要作用。外毒素T （ExoT）是唯一在所有表达T3SS的铜绿假单胞菌菌株中表达的T3SS效应蛋白。在这里，我们发现T3SS识别导致Abl / PKCδ / NLRC4参与的快速磷酸化级联反应，导致NLRC4炎症小体激活，最终导致炎症反应，限制伤口中的铜绿假单胞菌感染。我们进一步证明，ExoT作为铜绿假单胞菌的主要抗炎剂，通过靶向CrkII阻断Abl / PKCδ / NLRC4的磷酸化级联反应，我们进一步证明了CrkII在T3SS和铜绿假单胞菌感染时对Abl转激活和NLRC4炎性体激活很重要。铜绿假单胞菌分泌毒素ExoT，在发病过程中起重要作用。在这里，作者表明ExoT在伤口感染期间抑制nlrc4依赖性炎症反应。
Type 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, including Pseudomonas aeruginosa. Exotoxin T (ExoT) is the only T3SS effector protein that is expressed in all T3SS-expressing P. aeruginosa strains. Here we show that T3SS recognition leads to a rapid phosphorylation cascade involving Abl / PKCδ / NLRC4, which results in NLRC4 inflammasome activation, culminating in inflammatory responses that limit P. aeruginosa infection in wounds. We further show that ExoT functions as the main anti-inflammatory agent for P. aeruginosa in that it blocks the phosphorylation cascade through Abl / PKCδ / NLRC4 by targeting CrkII, which we further demonstrate to be important for Abl transactivation and NLRC4 inflammasome activation in response to T3SS and P. aeruginosa infection. Pseudomonas aeruginosa secretes the toxin ExoT, which is important for pathogenesis. Here, the authors show that ExoT inhibits NLRC4-dependent inflammatory responses during wound infection.
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