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
Journal of Leukocyte Biology | WILEY | Published : 2019
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 resp..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
This work was supported by the National Health and Medical Research Council of Australia (Fellowship 1141131 and Project Grant 1064945 to K.S.), the Australian Research Council (Fellowship FT130100361, and Project DP160102702 to K.S.), The University of Queensland (Postdoctoral Fellowship to D. Boucher, UQ Centennial Scholarship to D. Bierschenk), the Australian Government Department of Education and Training (International Postgraduate Research Scholarship to D. Bierschenk), and the Fonds de Recherche du Quebec en Sante (Postdoctoral Fellowship to D. Boucher). S.L.M acknowledges funding from National Health and Medical Research Council of Australia (Grants 1144282 and 1142354), The Sylvia and Charles Viertel Foundation, HHMI-Wellcome International Research Scholarship, and GlaxoSmithKline. We thank Associate Professor Petr Broz (University of Lausanne) for supplying the Salmonella Delta SPI1/Delta SPI2 mutant strain, and Professors Matthew Cooper and Avril Robertson for supplying MCC950.