The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

Published online
doi:10.1084/jem.20090741
The Journal of Experimental Medicine, Vol. 206, No. 10, 2179-2189
The Rockefeller University Press, 0022-1007 $30.00
© Carvalho et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2009K)
Right arrow PDF+supp data (2448K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Carvalho, F. A.
Right arrow Articles by Darfeuille-Michaud, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carvalho, F. A.
Right arrow Articles by Darfeuille-Michaud, A.
Related Collections
Right arrowRelated Article
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM

Frédéric A. Carvalho1, Nicolas Barnich1,2, Adeline Sivignon1,2, Claude Darcha3, Carlos H.F. Chan4, Clifford P. Stanners5, and Arlette Darfeuille-Michaud1,2

1 Université Clermont 1, Pathogénie Bactérienne Intestinale, JE2526, Unité Sous Contrat Institut National de la Recherche Agronomique 2018, Clermont-Ferrand F-63001, France
2 Institut Universitaire de Technologie en Génie Biologique, Aubière F-63172, France
3 Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire, Clermont-Ferrand F-63001, France
4 Department of Surgery and 5 Department of Biochemistry and McGill Cancer Centre, McGill University, Montréal, Québec, Canada

CORRESPONDENCE Nicolas Barnich: nicolas.barnich{at}u-clermont1.fr OR Arlette Darfeuille-Michaud: arlette.darfeuille-michaud{at}u-clermont1.fr

Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coli K-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severe colitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence of erosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression. The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAM expression because no sign of colitis was observed in transgenic mice infected with type 1 pili–negative LF82-{Delta}fimH isogenic mutant or in wild-type mice infected with AIEC LF82 bacteria. These findings strongly support the hypothesis that in CD patients having an abnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression can colonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesion to gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD.


F.A. Carvalho and N. Barnich contributed equally to this paper.

Abbreviations used: AIEC, adherent-invasive E. coli; CD, Crohn' disease; CEACAM, carcinoembryonic antigen-related cell adhesion molecule; CMC, carboxymethyl cellulose; DAI, disease activity index; GI, gastrointestinal; IBD, inflammatory bowel disease.

© 2009 Carvalho et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article

Clingy bacteria and Crohn's disease
Mitch Leslie
J. Exp. Med. 2009 206: 2055. [Full Text] [PDF]





  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS