The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute <em>Salmonella</em> challenge — ASN Events

The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge (#165)

Kaiwen Chen 1 , Christina J. Groß 2 , Flor Vásquez Sotomayor 1 , Katryn J. Stacey 1 , Jurg Tschopp 2 , Matthew J. Sweet 1 , Kate Schroder 1
  1. University of QLD, St Lucia, QLD, Australia
  2. University of Lausanne, Lausanne, Switzerland

The macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella, by eliciting caspase-1-dependent pro-inflammatory cytokine production (e.g. interleukin (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 amongst 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 pro-inflammatory and antimicrobial responses during pathogen challenge. Cell Reports (in press).