NEW YORK (Reuters Health) – The interaction of Escherichia coli adhesin molecule with CD55 molecules on the intestinal epithelial cell's surface induces a rapid increase in the immune-cell activating molecule called MICA, French investigators report. MICA induction in turn triggers interferon-gamma release by natural killer cells, and may thus contribute to the development of inflammatory bowel disease (IBD) in some individuals.
In the Proceedings of the National Academy of Science early online edition for February 5, Dr. Antoine Toubert and colleagues describe MICA as a polymorphic molecule that is a distant homolog of major histocompatability class I molecules expressed in normal intestinal epithelium.
The researchers showed that diffusely adherent E. coli increase MICA cell-surface expression on both the cervical carcinoma cell line HeLa and the human colorectal adenocarcinoma cell line Caco-2. E. coli's adhesin molecule AfaE was found to bind to the cellular receptor CD55, which triggered the MICA expression. MICA "are ligands of the NKG2D activating receptor" on natural killer cells, and this interaction resulted in interferon-gamma production.
In surgically resected colonic specimens of six control subjects, weak immunohistochemical staining of MICA was confined to the basal part of the glandular epithelial cells. However, in specimens from 18 patients with Crohn's disease, intense MICA immunostaining was observed on the whole epithelium extending to the deeper part of the glandular crypts.
The researchers conclude that the findings "implicate a bacterial trigger" for IBD in genetically susceptible individuals. "It is conceivable that other human enteric pathogens, especially enteroviruses, which also use CD55 for cell entry such as coxsackieviruses or echoviruses, could behave similarly" to the Afa-expressing strains of E. coli.