Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA.
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 gammadelta T cells, CD8+ alphabeta 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-gamma 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.
Tieng
Vannary
V
Laboratoire d'Immunologie et d'Histocompatibilité, Institut National de la Santé et de la Recherche Médicale Unit 396, Hôpital Saint-Louis, AP-HP, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Le Bouguénec
Chantal
C
du Merle
Laurence
L
Bertheau
Philippe
P
Desreumaux
Pierre
P
Janin
Anne
A
Charron
Dominique
D
Toubert
Antoine
A
D018830:Adhesins, Escherichia coli / Q000378:metabolism*; D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism*; D019556:COS Cells; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009876:Operon; D011485:Protein Binding
D018830:Adhesins, Escherichia coli; C108509:AfaE protein, E coli; D018958:CD55 Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D007371:Interferon-gamma