Open AccessThe Salmonella enterica serotype Typhi regulator TviA reduces interleukin‐8 production in intestinal epithelial cells by repressing flagellin secretion
Author(s) -
Winter Sebastian E.,
Raffatellu Manuela,
Wilson R. Paul,
Rüssmann Holger,
Bäumler Andreas J.
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01037.x
Subject(s) - flagellin , biology , salmonella enterica , salmonella typhi , secretion , microbiology and biotechnology , interleukin 8 , mutant , gene , escherichia coli , immunology , cytokine , genetics , biochemistry
Summary 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.