CEACAM6 Acts as a Receptor for Adherent-Invasive E. Coli, Supporting Ileal Mucosa Colonization in Crohn Disease

J Clin Invest. 2007 Jun;117(6):1566-74. doi: 10.1172/JCI30504. Epub 2007 May 24.

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-gamma or TNF-alpha stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Bacterial Adhesion
  • Base Sequence
  • Case-Control Studies
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Crohn Disease / immunology*
  • Crohn Disease / microbiology*
  • Escherichia coli / pathogenicity*
  • Female
  • GPI-Linked Proteins
  • Humans
  • Ileum / immunology
  • Ileum / microbiology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Male
  • Microvilli / immunology
  • Microvilli / microbiology
  • Middle Aged
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • Antigens, CD
  • CEACAM6 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • RNA, Small Interfering
  • Recombinant Proteins