The Salmonella pathogenicity island-2 subverts human NLRP3 and NLRC4 inflammasome responses
Journal Title
Journal of Leukocyte Biology
Publication Type
Journal Article in press
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-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.
Publisher
Wiley
WEHI Research Division(s)
Inflammation
PubMed ID
30368901
NHMRC Grants
NHMRC/1141131 NHMRC/1064945
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-11-20 09:12:47
Last Modified: 2018-11-20 11:37:41
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