Salmonella enterica Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation | Zendy

Sebastian Winter | Zendy; Maria G. Winter | Zendy; Victor Poon | Zendy; A. Marijke Keestra | Zendy; Torsten Sterzenbach | Zendy; Franziska Faber | Zendy; Luciana Fachini da Costa | Zendy; Fabiane Cassou | Zendy; É.A. Costa | Zendy; Geraldo Eleno Silveira Alves | Zendy; Tatiane A. Paíxão | Zendy; Renato L. Santos | Zendy; Andreas J. Bäumler | Zendy

Open Access

Salmonella enterica Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation

Author(s) -

Sebastian Winter,

Maria G. Winter,

Victor Poon,

A. Marijke Keestra,

Torsten Sterzenbach,

Franziska Faber,

Luciana Fachini da Costa,

Fabiane Cassou,

É.A. Costa,

Geraldo Eleno Silveira Alves,

Tatiane A. Paíxão,

Renato L. Santos,

Andreas J. Bäumler

Publication year - 2014

Publication title -

plos pathogens

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.719

H-Index - 206

eISSN - 1553-7374

pISSN - 1553-7366

DOI - 10.1371/journal.ppat.1004207

Subject(s) - type three secretion system , salmonella enterica , microbiology and biotechnology , biology , secretion , innate immune system , immune system , salmonella typhi , virulence , salmonella , typhoid fever , gene , bacteria , immunology , escherichia coli , genetics , biochemistry

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.

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