TY - JOUR
T1 - The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion
AU - Winter, Sebastian E.
AU - Raffatellu, Manuela
AU - Wilson, Paul R.
AU - Rüssmann, Holger
AU - Bäumler, Andreas J.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1462-5822.2007.01037.x
DO - 10.1111/j.1462-5822.2007.01037.x
M3 - Article
C2 - 17725646
AN - SCOPUS:36949010361
SN - 1462-5814
VL - 10
SP - 247
EP - 261
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 1
ER -