title: The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge.
abstract: The macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella by eliciting caspase-1-dependent proinflammatory cytokine production (e.g., interleukin-1β [IL-1β]) and pyroptotic cell death. However, the potential contribution of other cell types to inflammasome-mediated host defense against Salmonella was unclear. Here, we demonstrate that neutrophils, typically viewed as cellular targets of IL-1β, themselves activate the NLRC4 inflammasome during acute Salmonella infection and are a major cell compartment for IL-1β production during acute peritoneal challenge in vivo. Importantly, unlike macrophages, neutrophils do not undergo pyroptosis upon NLRC4 inflammasome activation. The resistance of neutrophils to pyroptotic death is unique among inflammasome-signaling cells so far described and allows neutrophils to sustain IL-1β production at a site of infection without compromising the crucial inflammasome-independent antimicrobial effector functions that would be lost if neutrophils rapidly lysed upon caspase-1 activation. Inflammasome pathway modification in neutrophils thus maximizes host proinflammatory and antimicrobial responses during pathogen challenge.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
authors.forename: Kaiwen W
authors.initials: KW
authors.lastname: Chen
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Groß
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
authors.forename: Flor Vásquez
authors.initials: FV
authors.lastname: Sotomayor
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia; Australian Infectious Disease Research Centre, The University of Queensland, St Lucia 4072, Australia.
authors.forename: Katryn J
authors.initials: KJ
authors.lastname: Stacey
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Jurg
authors.initials: J
authors.lastname: Tschopp
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia; Australian Infectious Disease Research Centre, The University of Queensland, St Lucia 4072, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sweet
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia; Australian Infectious Disease Research Centre, The University of Queensland, St Lucia 4072, Australia. Electronic address: k.schroder@imb.uq.edu.au.
authors.forename: Kate
authors.initials: K
authors.lastname: Schroder
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D020170:Caspase 1