Journal article
Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM
The Journal of experimental medicine, Vol.206(10), pp.2179-2189
09/28/2009
DOI: 10.1084/jem.20090741
PMCID: PMC2757893
PMID: 19737864
Abstract
Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epitheliumin Crohn’s disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherentinvasiveEscherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic miceexpressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coliK-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severecolitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence oferosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression.The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAMexpression because no sign of colitis was observed in transgenic mice infected with type 1pili–negative LF82-fimH isogenic mutant or in wild-type mice infected with AIEC LF82bacteria. These findings strongly support the hypothesis that in CD patients having anabnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression cancolonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesionto gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD.
Details
- Title: Subtitle
- Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM
- Creators
- Frédéric Carvalho - Pathogénie Bactérienne IntestinaleNicolas BARNICH - Pathogénie Bactérienne IntestinaleAdeline Sivignon - Pathogénie Bactérienne IntestinaleClaude Darcha - Service d'Anatomie et de Cytologie Pathologiques [CHU de Clermont-Ferrand]Carlos Chan - Department of Surgery [Montréal]Clifford Stanners - Department of Biochemistry [Montréal]Arlette Darfeuille-Michaud - Pathogénie Bactérienne Intestinale
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.206(10), pp.2179-2189
- Publisher
- Rockefeller University Press
- DOI
- 10.1084/jem.20090741
- PMID
- 19737864
- PMCID
- PMC2757893
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 09/28/2009
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984046802902771
Metrics
28 Record Views