The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi

Sebastian E. Winter, Maria G. Winter, Vidya Atluri, Victor Poon, Everton L. Romão, Renee M Tsolis, Andreas J Baumler

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To discern virulent from innocuous microbes, the innate immune system senses events associated with bacterial access to immunoprivileged sites such as the host cell cytosol. One such pathway is triggered by the cytosolic delivery of flagellin, the major subunit of the flagellum, by bacterial secretion systems. This leads to inflammasome activation and subsequent proinflammatory cell death (pyroptosis) of the infected phagocyte. In this study, we demonstrate that the causative agent of typhoid fever, Salmonella enterica serovar Typhi, can partially subvert this critical innate immune recognition event. The transcriptional regulator TviA, which is absent from Salmonella serovars associated with human gastroenteritis, repressed the expression of flagellin during infection of human macrophage-like (THP-1) cells. This mechanism allowed S. Typhi to dampen inflammasome activation, leading to reduced interleukin-1β (IL-1β) secretion and diminished cell death. Likewise, the introduction of the tviA gene in nontyphoidal Salmonella enterica serovar Typhimurium reduced flagellin-induced pyroptosis. These data suggest that gene regulation of virulence factors enables S. Typhi to evade innate immune recognition by concealing a pathogen-induced process from being sensed by the inflammasome.

Original languageEnglish (US)
Pages (from-to)1546-1555
Number of pages10
JournalInfection and Immunity
Volume83
Issue number4
DOIs
StatePublished - 2015

Fingerprint

Inflammasomes
Flagellin
Salmonella typhi
Bacterial Secretion Systems
Cell Death
Salmonella enterica
Flagella
Typhoid Fever
Gastroenteritis
Virulence Factors
Phagocytes
Interleukin-1
Salmonella
Cytosol
Genes
Immune System
Macrophages
Infection
Pyroptosis
Serogroup

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi. / Winter, Sebastian E.; Winter, Maria G.; Atluri, Vidya; Poon, Victor; Romão, Everton L.; Tsolis, Renee M; Baumler, Andreas J.

In: Infection and Immunity, Vol. 83, No. 4, 2015, p. 1546-1555.

Research output: Contribution to journalArticle

Winter, Sebastian E. ; Winter, Maria G. ; Atluri, Vidya ; Poon, Victor ; Romão, Everton L. ; Tsolis, Renee M ; Baumler, Andreas J. / The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi. In: Infection and Immunity. 2015 ; Vol. 83, No. 4. pp. 1546-1555.
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