Role of bacterial intimin in colonic hyperplasia and inflammation

Enteropathogenic Escherichia coli (EPEC) cells adhere to gut epithelial cel ls through intimin alpha: the ligand for a bacterially derived epithelial t ransmembrane protein called the translocated intimin receptor, Citrobacter rodentium colonizes the mouse colon in a similar fashion and uses a differe nt intimin: intimin beta. Intimin alpha was found to costimulate submitogen ic signals through the T cell receptor. Dead intimin beta(+) C. rodentium, intimin a-transfected C. rodentium or E. coli strain K12, and EPEC induced mucosal hyperplasia identical to that caused by C. rodentium live infection , as well as a massive T helper cell-type 1 immune response in the colonic mucosa, Mutation of cysteine-937 of intimin to alanine reduced costimulator y activity in vitro and prevented immunopathology in vivo. The mucosal chan ges elicited by C. rodentium were interferon-gamma-dependent. Immunopatholo gy induced by intimin enables the bacteria to promote conditions that are f avorable for increased microbial colonization.