In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 7 ( 2022-7-18), p. e1010305-
Abstract:
Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa ( P . aeruginosa ) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P . aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P . aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1β secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P . aeruginosa -induced GSDMD activation triggers Calcium-dependent and Peptidyl Arginine Deaminase-4-driven histone citrullination and translocation of neutrophil DNA into the cell cytosol without inducing extracellular Neutrophil Extracellular Traps. Finally, we show that neutrophil Caspase-1 contributes to IL-1β production and susceptibility to pyroptosis-inducing P . aeruginosa strains in vivo . Overall, we demonstrate that neutrophils are not universally resistant for Caspase-1-dependent pyroptosis.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010305
DOI:
10.1371/journal.ppat.1010305.g001
DOI:
10.1371/journal.ppat.1010305.g002
DOI:
10.1371/journal.ppat.1010305.g003
DOI:
10.1371/journal.ppat.1010305.g004
DOI:
10.1371/journal.ppat.1010305.g005
DOI:
10.1371/journal.ppat.1010305.s001
DOI:
10.1371/journal.ppat.1010305.s002
DOI:
10.1371/journal.ppat.1010305.s003
DOI:
10.1371/journal.ppat.1010305.s004
DOI:
10.1371/journal.ppat.1010305.s005
DOI:
10.1371/journal.ppat.1010305.s006
DOI:
10.1371/journal.ppat.1010305.s007
DOI:
10.1371/journal.ppat.1010305.s008
DOI:
10.1371/journal.ppat.1010305.s009
DOI:
10.1371/journal.ppat.1010305.s010
DOI:
10.1371/journal.ppat.1010305.s011
DOI:
10.1371/journal.ppat.1010305.r001
DOI:
10.1371/journal.ppat.1010305.r002
DOI:
10.1371/journal.ppat.1010305.r003
DOI:
10.1371/journal.ppat.1010305.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
Permalink