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

• Main Authors: Sebastian E Winter, Maria G Winter, Victor Poon, A Marijke Keestra, Torsten Sterzenbach, Franziska Faber, Luciana F Costa, Fabiane Cassou, Erica A Costa, Geraldo E S Alves, Tatiane A Paixão, Renato L Santos, Andreas J Bäumler
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-07-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC4081808?pdf=render

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 (T3SS-1) and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-κB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium) suppressed T3SS-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.