The Salmonella pathogenicity island-2 subverts human NLRP3 and NLRC4 inflammasome responses
- Bierschenk, D; Monteleone, M; Moghaddas, F; Baker, PJ; Masters, SL; Boucher, D; Schroder, K;
- Journal Title
- Journal of Leukocyte Biology
- Publication Type
- Journal Article in press
- 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-1beta production and macrophage death. Inactivation of the SPI1 T3SS diminished human macrophage responses to WT and DeltaSPI2 Salmonella. Salmonella DeltaSPI2 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-1beta 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.
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-11-20 09:12:47Last Modified: 2018-11-20 11:37:41