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

Here the Inflammasome Lab reveal that Salmonella evades immune response by subverting the NLRP3 and NLRC4 inflammasome in macrophages.

Damien Bierschenk, Mercedes Monteleone, Fiona Moghaddas, Seth L. Masters, Dave Boucher, Kate Schroder. (2018).
The Salmonella pathogenicity island‐2 subverts human NLRP3 and NLRC4 inflammasome responses. Journal of Leukocyte Biology 2019;105:401–410. Pubmed

 

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.

 

Image: The Gram‐negative bacterium Salmonella Typhimurium suppresses human macrophage inflammasome responses via the Salmonella Pathogenicity Island 2.

 

 

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ABOUT Inflammasome Lab

Inflammasome Lab is a group of researchers led by Dr Kate Schroder at the Institute for Molecular Bioscience, The University of Queensland.
We seek to unravel the secrets of inflammasomes – protein complexes at the heart of inflammation and disease – to allow for new therapies to fight human diseases.