CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT

Autor: Mohamed F, Mohamed, Kajal, Gupta, Josef W, Goldufsky, Ruchi, Roy, Lauren T, Callaghan, Dawn M, Wetzel, Timothy M, Kuzel, Jochen, Reiser, Sasha H, Shafikhani
Rok vydání: 2020
Předmět:
Zdroj: Nature communications. 13(1)
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE