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

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. 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 / PKC delta / 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 / PKC delta / 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.

Automated summary

Pseudomonas aeruginosa secretes ExoT, a toxin that inhibits NLRC4-dependent inflammatory responses during wound infection. The T3SS recognition leads to phosphorylation cascade involving Abl/PKC delta/NLRC4, which activates NLRC4 inflammasome and initiates inflammatory responses to limit P. aeruginosa infection. ExoT functions as the main anti-inflammatory agent by targeting CrkII and blocking the phosphorylation cascade.