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

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...

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Autores principales: Jameel Batah, Hussein Kobeissy, Phuong Trang Bui Pham, Cécile Denève-Larrazet, Sarah Kuehne, Anne Collignon, Claire Janoir-Jouveshomme, Jean-Christophe Marvaud, Imad Kansau
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/5b9cae09e7414f9d900cc05bf5041ee6
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spelling oai:doaj.org-article:5b9cae09e7414f9d900cc05bf5041ee62021-12-02T12:30:45ZClostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins10.1038/s41598-017-03621-z2045-2322https://doaj.org/article/5b9cae09e7414f9d900cc05bf5041ee62017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03621-zhttps://doaj.org/toc/2045-2322Abstract 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.Jameel BatahHussein KobeissyPhuong Trang Bui PhamCécile Denève-LarrazetSarah KuehneAnne CollignonClaire Janoir-JouveshommeJean-Christophe MarvaudImad KansauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jameel Batah
Hussein Kobeissy
Phuong Trang Bui Pham
Cécile Denève-Larrazet
Sarah Kuehne
Anne Collignon
Claire Janoir-Jouveshomme
Jean-Christophe Marvaud
Imad Kansau
Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
description 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.
format article
author Jameel Batah
Hussein Kobeissy
Phuong Trang Bui Pham
Cécile Denève-Larrazet
Sarah Kuehne
Anne Collignon
Claire Janoir-Jouveshomme
Jean-Christophe Marvaud
Imad Kansau
author_facet Jameel Batah
Hussein Kobeissy
Phuong Trang Bui Pham
Cécile Denève-Larrazet
Sarah Kuehne
Anne Collignon
Claire Janoir-Jouveshomme
Jean-Christophe Marvaud
Imad Kansau
author_sort Jameel Batah
title Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
title_short Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
title_full Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
title_fullStr Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
title_full_unstemmed Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
title_sort clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/5b9cae09e7414f9d900cc05bf5041ee6
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