PLoS Pathogens (Jul 2014)

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

  • 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

DOI
https://doi.org/10.1371/journal.ppat.1004207
Journal volume & issue
Vol. 10, no. 7
p. e1004207

Abstract

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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.