Role of Bacterial Intimin in Colonic Hyperplasia and Inflammation

Abstract

Enteropathogenic Escherichia coli (EPEC) cells adhere to gut epithelial cells through intimin α: the ligand for a bacterially derived epithelial transmembrane protein called the translocated intimin receptor. Citrobacter rodentium colonizes the mouse colon in a similar fashion and uses a different intimin: intimin β. Intimin α was found to costimulate submitogenic signals through the T cell receptor. Dead intimin β + C. rodentium , intimin α–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 costimulatory activity in vitro and prevented immunopathology in vivo. The mucosal changes elicited by C. rodentium were interferon-γ–dependent. Immunopathology induced by intimin enables the bacteria to promote conditions that are favorable for increased microbial colonization.