Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells

Jameel Batah, Cécile Denève-Larrazet, Pierre-Alain Jolivot, Sarah Kuehne, Anne Collignon, Jean-Christophe Marvaud, Imad Kansau

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Clostridium difficile has become the most common enteropathogen responsible for intestinal nosocomial post-antibiotic infections. This has coincided with the appearance of serious cases related to the emergence of hypervirulent strains. The toxins are the main virulence factors and elicit an inflammatory response during C. difficile infection. However, other bacterial components appear to be involved in the inflammatory process. In some pathogens, flagella play a role in pathogenesis through abnormal stimulation of the TLR5-mediated host immune response. To date, few studies have addressed this role for C. difficile flagella. In the current study, we confirm in two different epithelial cell models that C. difficile thanks to its FliC flagellin interacts with TLR5. In addition, thanks to inhibition and transcriptomic studies we demonstrate that the interaction of flagellin and TLR5 predominantly activates the NF-κB and, in a lesser degree, the MAPK pathways, via TLR5, leading to up-regulation of pro-inflammatory gene expression and synthesis of pro-inflammatory mediators. These results suggest a role for C. difficile flagella in contributing to inflammatory response in host intestinal cells.

Original languageEnglish
Pages (from-to)116-124
Number of pages9
JournalAnaerobe
Volume38
DOIs
Publication statusPublished - Apr 2016

Keywords

  • Animals
  • Cell Line
  • Cells, Cultured
  • Clostridium Infections
  • Clostridium difficile
  • Cytokines
  • Epithelial Cells
  • Flagella
  • Flagellin
  • Gene Expression
  • Humans
  • Mutation
  • NF-kappa B
  • Signal Transduction
  • Toll-Like Receptor 5
  • Journal Article
  • Research Support, Non-U.S. Gov't

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