@article{8e67dcd467474b3c9408ba96ccefe73d,
title = "CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT",
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.",
author = "Mohamed, {Mohamed F.} and Kajal Gupta and Goldufsky, {Josef W.} and Ruchi Roy and Callaghan, {Lauren T.} and Wetzel, {Dawn M.} and Kuzel, {Timothy M.} and Jochen Reiser and Shafikhani, {Sasha H.}",
note = "Funding Information: We would like to thank Dr. Vishva Dixit and Genentech for their generous gifts of ASC and Nlrc4 knockout mice and for NLRC4 BMDM and the expression vectors. We also would like to thank Dr. Alan Hauser (Northwestern University) for providing P. aeruginosa wound clinical isolates, and the rest of Shafikhani lab members for their valued opinions on these studies. This work was supported by the National Institutes of Health (NIH) grants RO1DK107713 and R21AI110685-01 (both to S.H.S.), and R01AI146349 and Welch Foundation I-2086 (to D.M.W.). −/− −/− –/– Funding Information: We would like to thank Dr. Vishva Dixit and Genentech for their generous gifts of ASC?/? and Nlrc4?/? knockout mice and for NLRC4?/? BMDM and the expression vectors. We also would like to thank Dr. Alan Hauser (Northwestern University) for providing P. aeruginosa wound clinical isolates, and the rest of Shafikhani lab members for their valued opinions on these studies. This work was supported by the National Institutes of Health (NIH) grants RO1DK107713 and R21AI110685-01 (both to S.H.S.), and R01AI146349 and Welch Foundation I-2086 (to D.M.W.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-28967-5",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}