Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 Access content directly
Journal Articles PLoS Pathogens Year : 2022

Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa

Nathalie Winter

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.

Domains

Immunology
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hal-03738417 , version 1 (05-09-2022)

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Karin Santoni, David Pericat, Leana Gorse, Julien Buyck, Miriam Pinilla, et al.. Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. PLoS Pathogens, 2022, 18 (7), pp.e1010305. ⟨10.1371/journal.ppat.1010305⟩. ⟨hal-03738417⟩
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