Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium

Cell Rep. 2020 Jul 28;32(4):107967. doi: 10.1016/j.celrep.2020.107967.


Either caspase-1 or caspase-11 can cleave gasdermin D to cause pyroptosis, eliminating intracellular replication niches. We previously showed that macrophages detect Burkholderia thailandensis via NLRC4, triggering the release of interleukin (IL)-18 and driving an essential interferon (IFN)-γ response that primes caspase-11. We now identify the IFN-γ-producing cells as a mixture of natural killer (NK) and T cells. Although both caspase-1 and caspase-11 can cleave gasdermin D in macrophages and neutrophils, we find that NLRC4-activated caspase-1 triggers pyroptosis in macrophages, but this pathway does not trigger pyroptosis in neutrophils. In contrast, caspase-11 triggers pyroptosis in both macrophages and neutrophils. This translates to an absolute requirement for caspase-11 in neutrophils during B. thailandensis infection in mice. We present an example of inflammasome sensors causing diverging outcomes in different cell types. Thus, cell fates are dictated not simply by the pathogen or inflammasome, but also by how the cell is wired to respond to detection events.

Keywords: Burkholderia thailandensis; NK cells; NLRC4; caspase-1; caspase-11; cytosol-invasive pathogen; inflammasome; neutrophil; pyropotosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Burkholderia / pathogenicity
  • Calcium-Binding Proteins / metabolism
  • Caspase 1 / metabolism
  • Caspases / metabolism
  • Caspases, Initiator / metabolism*
  • Cytosol / metabolism
  • Female
  • Inflammasomes / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / metabolism*
  • Neutrophils / microbiology
  • Phosphate-Binding Proteins / metabolism
  • Pyroptosis / immunology
  • Pyroptosis / physiology*


  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Gsdmd protein, mouse
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Phosphate-Binding Proteins
  • Casp4 protein, mouse
  • Caspases
  • Caspases, Initiator
  • Caspase 1

Supplementary concepts

  • Burkholderia thailandensis