Authors
Sebastian E. Winter, Maria G. Winter, Vidya Atluri, Victor Poon, Everton L. Romão, Renée M. Tsolis, and Andreas J. Bäumler.
Abstract
To discern virulent from innocuous microbes, the innate immune system senses events associated with bacterial access to immuno-privileged sites such as the host cell cytosol. One such pathway is triggered by cytosolic delivery of flagellin, the major subunit of the flagellum, by bacterial secretion systems. This leads to inflammasome activation and subsequent pro-inflammatory cell death (pyroptosis) of the infected phagocyte. In this study, we demonstrate that the causative agent of typhoid fever, Salmonella enterica serovar Typhi, can partially subvert this critical innate immune recognition event. The transcriptional regulator TviA, which is absent from Salmonella serovars associated with human gastroenteritis, repressed expression of flagellin during infection of human macrophage-like (THP-1) cells. This mechanism allowed S. Typhi to dampen inflammasome activation, leading to reduced interleukin (IL)-1β secretion and diminished cell death. Likewise, introduction of the tviA gene in the non-typhoidal S. enterica serovar Typhimurium reduced flagellin-induced pyroptosis. These data suggest that gene regulation of virulence factors enables S. Typhi to evade innate immune recognition by concealing a pathogen-induced process from being sensed by the inflammasome.
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