By the same authors

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From the same journal

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

Research output: Contribution to journalArticlepeer-review

Author(s)

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

Department/unit(s)

Publication details

JournalJournal of leukocyte biology
DateAccepted/In press - 15 Sep 2018
DateE-pub ahead of print (current) - 4 Oct 2018
Issue number2
Volume105
Number of pages10
Pages (from-to)401-410
Early online date4/10/18
Original languageEnglish

Abstract

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.

Bibliographical note

©2018 Society for Leukocyte Biology.

    Research areas

  • 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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