Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation.

[typhoid]

Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses . Here we show that Salmonella enterica serovar Typhi (S . Typhi ), the causative agent of typhoid fever , tightly regulates expression of the invasion-associated type III secretion system (T 3 SS-1 ) and thus fails to activate these innate immune signaling pathways . The S . Typhi regulatory protein TviA rapidly repressed T 3 SS-1 expression , thereby preventing RAC 1 -dependent , RIP 2 -dependent activation of NF-κB in epithelial cells . Heterologous expression of TviA in S . enterica serovar Typhimurium (S . Typhimurium ) suppressed T 3 SS-1 -dependent inflammatory responses generated early after infection in animal models of gastroenteritis . These results suggest that S . Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression .