Microbial and cellular interactions of flagellate pathogen Salmonella enterica serovar enteritidis and flagellate intestinal resident Roseburia sp with intestinal epithelial cells

Flagellin was demonstrated to initiate signalling responses in intestinal epithelial cells resulting in the induction of interleukin-8 (IL-8) and human beta defensin-2 (hBD-2) genes.  Intestinal epithelial cell responses to flagellin isolated from both these organisms and signalling responses to who...

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Bibliographic Details
Main Author: Fraser-Pitt, Douglas
Published: University of Aberdeen 2008
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Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446222
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Summary:Flagellin was demonstrated to initiate signalling responses in intestinal epithelial cells resulting in the induction of interleukin-8 (IL-8) and human beta defensin-2 (hBD-2) genes.  Intestinal epithelial cell responses to flagellin isolated from both these organisms and signalling responses to whole bacteria and their mutants was examined. Studies with <i>S. enteritidis </i>mutants confirmed the importance of flagellin in signalling responses in Caco-2 intestinal epithelial cells.  Flagellin was a requirement for the nuclear locations of the transcription factor NF-κB.  IL-8 and hBD-2 gene transcription in response to <i>S. enteritidis </i>was found to be dependent on bacterial cell density.  At high densities there was a down-regulation in the induction of these genes.  This down-regulatory signal was isolated in bacterial cell-free conditioned media.  Experiments with <i>R. intestinalis </i>in a novel anaerobic/aerobic co-culture system also suggested that this organism may regulate aspects of the intestinal epithelial cell response to flagellin.  Proteomic methods were employed to characterise proteins in bacterial cell-free conditioned media produced by <i>S. enteritidis,</i> and also to examine density-dependent changes in the <i>S. enteritidis </i>proteome.  These techniques were also employed to investigate epithelial cell-induced changes in the proteome of flagellate commensal <i>Roseburia hominis.</i> In summary this study confirmed previous published evidence that flagellin is important in signalling responses in Caco-2 cells challenged with <i>S. enteritidis. </i>Novel experiments with commensal <i>R. intestinalis </i>derived flagellin (<i>fliC</i> gene sequenced in this project) showed that it also induced the transcription of IL-8 and hBD-2 genes.