Binding of Escherichia coli Adhesin AfaE to CD55 Triggers Cell-Surface Expression of the MHC Class I-Related Molecule MICA

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-03, Vol.99 (5), p.2977-2982
• Main Authors: Tieng, Vannary, Le Bouguénec, Chantal, du Merle, Laurence, Bertheau, Philippe, Desreumaux, Pierre, Janin, Anne, Charron, Dominique, Toubert, Antoine
• Format: Article
• Language: English
• Subjects: Adhesins, Escherichia coli - metabolism; AfaE protein; Animals; Antiserum; Bacteria; Biological Sciences; Caco 2 cells; CD55 antigen; CD55 Antigens - metabolism; Cell lines; Cell Membrane - metabolism; Cells; Chlorocebus aethiops; Colon - metabolism; Colon - pathology; COS Cells; Crohn Disease - metabolism; Crohn Disease - pathology; Crohn Disease - surgery; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Escherichia coli; Escherichia coli - metabolism; HeLa Cells; Histocompatibility Antigens Class I - biosynthesis; Humans; Immunoenzyme Techniques; Immunology; Interferon-gamma - biosynthesis; Killer Cells, Natural - metabolism; Membrane Proteins - metabolism; Mica; MICA antigen; MICA gene; Molecules; Natural killer cells; Operon; Protein Binding; T lymphocytes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.032668099

MICA are distant homologs of MHC class I molecules expressed in the normal intestinal epithelium. They are ligands of the NKG2D activating receptor expressed on most γδ T cells, CD8+ αβ T cells, and natural killer cells and therefore play a critical role in innate immune responses. We investigated MICA cell-surface expression on infection of epithelial cell lines by enteric bacteria and show here that MICA expression can be markedly increased by bacteria of the diffusely adherent Escherichia coli diarrheagenic group. This effect is mediated by the specific interaction between bacterial adhesin AfaE and its cellular receptor, CD55, or decay-accelerating factor. It is extremely rapid after AfaE binding, consistent with a stress-induced signal. MICA induction on epithelial cells triggered IFN-γ release by the NKG2D expressing natural killer cell line NKL. This host-bacteria interaction pathway could play a role in the pathogenesis of inflammatory bowel disease, a condition that implicates a bacterial trigger in genetically susceptible individuals. This was supported by the increased MICA expression at the surface of epithelial cells in colonic biopsies from Crohn's disease-affected patients compared with controls.