The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion

Cell Microbiol. 2008 Jan;10(1):247-61. doi: 10.1111/j.1462-5822.2007.01037.x.


Unlike non-typhoidal Salmonella serotypes, S. enterica serotype Typhi does not elicit neutrophilic infiltrates in the human intestinal mucosa. The Vi capsule-encoding tviABCDEvexABCDE operon (viaB locus) is a S. Typhi-specific DNA region preventing production of interleukin (IL)-8 during infection of intestinal epithelial cells. We elucidated the mechanism by which the viaB locus reduces IL-8 production in human colonic epithelial (T84) cells. A S. Typhi tviABCDEvexABCDE deletion mutant, but not a tviBCDEvexABCDE deletion mutant, elicited increased IL-8 production, which could be reduced to wild-type levels by introducing the cloned tviA regulatory gene. Thus, IL-8 expression in T84 cells was modulated by the TviA regulatory protein, but not by the Vi capsular antigen. Consistent with previous reports, IL-8 secretion by T84 cells was dependent on the presence of the flagellin protein FliC. TviA reduced expression of flhDC::lacZ and fliC::lacZ transcriptional fusions and secretion of FliC in S. Typhi. Introduction of tviA into S. enterica serotype Typhimurium reduced flagellin secretion and IL-8 expression. In conclusion, the viaB locus reduces IL-8 production in T84 cells by a TviA-mediated repression of flagellin secretion. Our data suggest that changes in flagella gene regulation played an important role during evolution of the human-adapted S. Typhi.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Artificial Gene Fusion
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Cell Line
  • Down-Regulation*
  • Epithelial Cells / microbiology*
  • Flagellin / biosynthesis*
  • Genes, Reporter
  • Genetic Complementation Test
  • Humans
  • Interleukin-8 / biosynthesis*
  • Salmonella typhi / genetics
  • Salmonella typhi / immunology*
  • Salmonella typhimurium / genetics
  • Sequence Deletion
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics


  • Bacterial Proteins
  • Interleukin-8
  • Transcription Factors
  • tviA protein, Salmonella typhi
  • Flagellin
  • beta-Galactosidase