TY - JOUR
T1 - Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa
AU - Santoni, Karin
AU - Pericat, David
AU - Gorse, Leana
AU - Buyck, Julien
AU - Pinilla, Miriam
AU - Prouvensier, Laure
AU - Bagayoko, Salimata
AU - Hessel, Audrey
AU - Leon-Icaza, Stephen Adonai
AU - Bellard, Elisabeth
AU - Mazères, Serge
AU - Doz-Deblauw, Emilie
AU - Winter, Nathalie
AU - Paget, Christophe
AU - Girard, Jean Philippe
AU - Pham, Christine T.N.
AU - Cougoule, Celine
AU - Poincloux, Renaud
AU - Lamkanfi, Mohamed
AU - Lefrançais, Emma
AU - Meunier, Etienne
AU - Planès, Rémi
N1 - Publisher Copyright:
© 2022 Santoni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85135596792&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1010305
DO - 10.1371/journal.ppat.1010305
M3 - Article
C2 - 35849616
AN - SCOPUS:85135596792
SN - 1553-7366
VL - 18
JO - PLoS pathogens
JF - PLoS pathogens
IS - 7
M1 - e1010305
ER -