CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease
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
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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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 2

Type 1 pili–mediated adhesion to the brush border of ileal enterocytes.

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Type 1 pili–mediated adhesion to the brush border of ileal enterocytes. ...
(A) Adhesion of the LF82-derived type 1 pili–negative mutant 52D11 (fimA::Tn5phoA) to the brush border of enterocytes isolated from CD patients and controls. (B) Adhesion of AIEC LF82 to the brush border of enterocytes isolated from CD patients and controls in the absence or presence of 2% d-mannose. (C) Adhesion of LF82 bacteria expressing type 1 pili variant and of nonpathogenic E. coli K-12 transformed with pPil38 to induce the expression of K-12 type 1 pili (left panel) or of LF82 bacteria expressing either LF82 type 1 pili variant or K-12 type 1 pili (middle panel) to the brush border of enterocytes isolated from CD patients. Western blot analysis using anti–type 1 pili antibodies performed on whole bacterial extracts showed similar amounts of type 1 pili expressed by the various strains (right panel). (D) Expression of a highly mannosylated molecule on the brush border of ileal enterocytes isolated from CD patients. Phase contrast microscopy and fluorescence labeling using ConA-FITC of ileal enterocytes from a CD patient and a control. Original magnification, ×400.