Abstract
Abstract Pattern recognition receptors-based sensing of microbial products and activities to mount an effective antibacterial defense is an evolutionarily conserved immune strategy. Cytosolic LPS sensing by caspase-11 or -4 and the ensuing noncanonical inflammasome-mediated IL-1 and cell death responses play a central role in the clearance of bacterial pathogens. In response to this selection pressure from the host it is natural that pathogens have developed strategies to actively antagonize or evade inflammasome responses. However, the mechanisms by which bacterial pathogens subvert the noncanonical inflammasome pathway is only beginning to be understood. In this context, this study investigates bacterial modulation of noncanonical inflammasome by utilizing Salmonella entericaserovar Typhimurium as a model enteric pathogen. By screening a library of defined single gene mutants of S. Typhimurium, we found that a mutant that lacks a Salmonella Pathogenicity Island 1 (SPI-1) effector triggers a markedly higher cell death and IL-1 responses in epithelial and professional innate immune cells indicating that this effector protein is a suppressor of inflammasome responses. Further characterization indicated that this effector protein-mediated inhibition of inflammasome responses occurs at the level of gasdermin D, the pyroptotic executioner. Together, this study attributes a novel inflammasome inhibitory function to a Salmonella SPI-1 effector.
Published Version
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