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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cell Death
  • Cells, Cultured
  • Humans
  • Immunity, Innate
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Peritonitis / immunology*
  • Salmonella Infections / immunology*


  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Ipaf protein, mouse
  • Caspase 1