The Salmonella pathogenicity island-2 subverts human NLRP3 and NLRC4 inflammasome responses

Damien Bierschenk, Mercedes Monteleone, Fiona Moghaddas, Paul J Baker, Seth L Masters, Dave Boucher, Kate Schroder

Research output: Contribution to journalArticlepeer-review


Inflammasomes are signaling hubs that activate inflammatory caspases to drive cytokine maturation and cell lysis. Inflammasome activation by Salmonella Typhimurium infection or Salmonella-derived molecules is extensively studied in murine myeloid cells. Salmonella-induced inflammasome signaling in human innate immune cells, is however, poorly characterized. Here, we show that Salmonella mutation to inactivate the Salmonella pathogenicity island-2 type III secretion system (SPI2 T3SS) potentiates S. Typhimurium-induced inflammasome responses from primary human macrophages, resulting in strong IL-1β production and macrophage death. Inactivation of the SPI1 T3SS diminished human macrophage responses to WT and ΔSPI2 Salmonella. Salmonella ΔSPI2 elicited a mixed inflammasome response from human myeloid cells, in which NLR family CARD-domain containing protein 4 (NLRC4) and NLR family PYRIN-domain containing protein 3 (NLRP3) perform somewhat redundant functions in generating IL-1β and inducing pyroptosis. Our data suggest that Salmonella employs the SPI2 T3SS to subvert SPI1-induced NLRP3 and NLRC4 inflammasome responses in human primary macrophages, in a species-specific immune evasion mechanism.

Original languageEnglish
Pages (from-to)401-410
Number of pages10
JournalJournal of leukocyte biology
Issue number2
Early online date4 Oct 2018
Publication statusE-pub ahead of print - 4 Oct 2018

Bibliographical note

©2018 Society for Leukocyte Biology.


  • Animals
  • CARD Signaling Adaptor Proteins/metabolism
  • Calcium-Binding Proteins/metabolism
  • Cell Death
  • Genomic Islands
  • Humans
  • Inflammasomes/metabolism
  • Interleukin-1beta/metabolism
  • Macrophages/metabolism
  • Mice, Inbred C57BL
  • Myeloid Cells/metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
  • Pyroptosis
  • Salmonella typhimurium/genetics

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