Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins

Jameel Batah, Hussein Kobeissy, Phuong Trang Bui Pham, Cécile Denève-Larrazet, Sarah Kuehne, Anne Collignon, Claire Janoir-Jouveshomme, Jean-Christophe Marvaud, Imad Kansau

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
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Abstract

Clostridium difficile is the most important enteropathogen involved in gut nosocomial post-antibiotic infections. The emergence of hypervirulent strains has contributed to increased mortality and morbidity of CDI. The C. difficile toxins contribute directly to CDI-associated lesions of the gut, but other bacterial factors are needed for the bacteria to adhere and colonize the intestinal epithelium. The C. difficile flagella, which confer motility and chemotaxis for successful intestinal colonization, could play an additional role in bacterial pathogenesis by contributing to the inflammatory response of the host and mucosal injury. Indeed, by activating the TLR5, flagella can elicit activation of the MAPK and NF-κB cascades of cell signaling, leading to the secretion of pro-inflammatory cytokines. In the current study, we demonstrate, by using an animal model of CDI, a synergic effect of flagella and toxins in eliciting an inflammatory mucosal response. In this model, the absence of flagella dramatically decreases the degree of mucosal inflammation in mice and the sole presence of toxins without flagella was not enough to elicit epithelial lesions. These results highlight the important role of C. difficile flagella in eliciting mucosal lesions as long as the toxins exert their action on the epithelium.

Original languageEnglish
Pages (from-to)3256
JournalScientific Reports
Volume7
Issue number1
Early online date12 Jun 2017
DOIs
Publication statusE-pub ahead of print - 12 Jun 2017

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