CrkII/Abl Phosphorylation Cascade is Critical for NLRC4 Inflammasome Activity and is Blocked by Pseudomonas Aeruginosa ExoT

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Mar 12

PMID 35277504

Authors

Mohamed F Mohamed

Kajal Gupta

Josef W Goldufsky

Ruchi Roy

Lauren T Callaghan

Dawn M Wetzel

Timothy M Kuzel

Jochen Reiser

Sasha H Shafikhani

Affiliations

Soon will be listed here.

Abstract

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.

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