Journal Article

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

Planès, Rémi, Universiteit Gent = Ghent University = Université de Gand (UGENT), European Project: 804249,INFLAME, Institut de pharmacologie et de biologie structurale (IPBS) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Prouvensier, Laure, Hessel, Audrey, Pinilla, Miriam, Pharmacologie des anti-infectieux et antibiorésistance [U 1070] (PHAR2 [Poitiers]) ; Université de Poitiers = University of Poitiers (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bagayoko, Salimata, Pham, Christine T.N, Mazères, Serge, Bellard, Elisabeth, Buyck, Julien, Infectiologie et Santé Publique (ISP) ; Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Doz-Deblauwe, Emilie, Meunier, Etienne, Gorse, Leana, Cougoule, Céline, Girard, Jean-Philippe, Lefrancais, Emma, Santoni, Karin, Winter, Nathalie, Washington University School of Medicine in St. Louis

2022

Overview

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.

• Publisher: CCSD,Public Library of Science,Public Library of Science (PLoS)
• Subject: Apoptosis / Bacteria / Bacterial infections / Biology and Life Sciences / Bone marrow / Calcium / Caspase-1 / Cell death / Cholera / Citrulline / Cytosol / Deoxyribonucleic acid / Development and progression / DNA / Exotoxins / Experiments / Flagellin / Health aspects / Histones / IL-1β / Immunology / Infections / Inflammasomes / Interleukins / Leukocytes (neutrophilic) / Life Sciences / Medical research / Medicine and Health Sciences / Medicine, Experimental / Microscopy / Neutrophils / Physiological aspects / Plasma / Pseudomonas aeruginosa / Pseudomonas aeruginosa infections / Pyroptosis / Research and Analysis Methods / Risk factors / Salmonella / Severe acute respiratory syndrome coronavirus 2 / Strains (organisms) / Translocation / Virulence
• ISBN: 0009713903000