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Cell Rep. 2014 Jul 24;8(2):570-82. doi: 10.1016/j.celrep.2014.06.028. Epub 2014 Jul 17.

The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge.

Author information

1
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
2
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
3
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.
4
Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
5
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.
6
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.

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.

PMID:
25043180
DOI:
10.1016/j.celrep.2014.06.028
[Indexed for MEDLINE]
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