CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease
Nicolas Barnich, … , Jean-Frédéric Colombel, Arlette Darfeuille-Michaud
Nicolas Barnich, … , Jean-Frédéric Colombel, Arlette Darfeuille-Michaud
Published June 1, 2007
Citation Information: J Clin Invest. 2007;117(6):1566-1574. https://doi.org/10.1172/JCI30504.
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Research Article Infectious disease

CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease

Abstract

The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal epithelial cells. Here, we show that CD-associated AIEC strains adhere to the brush border of primary ileal enterocytes isolated from CD patients but not controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1 pili expression on the bacterial surface and on carcinoembryonic antigen–related cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In addition, our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-γ or TNF-α stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients.

Authors

Nicolas Barnich, Frédéric A. Carvalho, Anne-Lise Glasser, Claude Darcha, Peter Jantscheff, Matthieu Allez, Harald Peeters, Gilles Bommelaer, Pierre Desreumaux, Jean-Frédéric Colombel, Arlette Darfeuille-Michaud

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Figure 3

CEACAM6 expression supports AIEC adhesion.

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CEACAM6 expression supports AIEC adhesion. (A) Western blot analysis of ...
(A) Western blot analysis of whole protein extracts from ileal biopsies taken in both involved and uninvolved areas of 9 CD patients and from 9 ileal biopsies from controls using anti-CEACAM5, anti-CEACAM6, and anti–β-actin antibodies. (B) Western blot analysis of whole protein extracts from colonic biopsies from 3 controls, 3 UC patients, and 3 CD patients using anti-CEACAM6 and anti–β-actin antibodies. (C) Adhesion indices of AIEC strain LF82 to the brush border of enterocytes from CD patients in the presence of monoclonal antibodies raised against CEACAM1, CEACAM5, CEACAM6, THP, and CD48. (D) Adhesion indices of AIEC strain LF82 to the brush border of enterocytes from 4 CD patients in the presence of anti-CEACAM6 monoclonal antibody. (E) Confocal microscopic analysis of HeLa cells transfected with human CEACAM6 cDNA cloned and infected with AIEC LF82 harboring a GFP construct. Original magnification, ×1,000. CEACAM6 expression was detected using anti-CEACAM6 monoclonal antibody and a Texas red–conjugated anti-mouse IgG. Arrows show clear colocalization (yellow staining) between CEACAM6 and bacteria.