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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kovacs, SB; Oh, C; Maltez, VI; McGlaughon, BD; Verma, A; Miao, EA; Aachoui, Y

Published Date

  • July 28, 2020

Published In

Volume / Issue

  • 32 / 4

Start / End Page

  • 107967 -

PubMed ID

  • 32726630

Pubmed Central ID

  • PMC7480168

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2020.107967


  • eng

Conference Location

  • United States