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

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1004207
JournalPLoS pathogens
Volume10
Issue number7
DOIs
StatePublished - Jul 2014

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Winter, S. E., Winter, M. G., Poon, V., Keestra, A. M., Sterzenbach, T., Faber, F., Costa, L. F., Cassou, F., Costa, E. A., Alves, G. E. S., Paixão, T. A., Santos, R. L., & Bäumler, A. J. (2014). Salmonella enterica Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation. PLoS pathogens, 10(7), [e1004207]. https://doi.org/10.1371/journal.ppat.1004207