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Science 23 July 1999:
Vol. 285. no. 5427, pp. 588 - 591
DOI: 10.1126/science.285.5427.588
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Reports

Role of Bacterial Intimin in Colonic Hyperplasia and Inflammation

Lisa M. Higgins, 1 Gad Frankel, 2 Ian Connerton, 3 Nathalie S. Gonçalves, 1 Gordon Dougan, 2 Thomas T. MacDonald 1

Enteropathogenic Escherichia coli (EPEC) cells adhere to gut epithelial cells through intimin alpha : 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 beta . Intimin alpha  was found to costimulate submitogenic signals through the T cell receptor. Dead intimin beta + C. rodentium, intimin alpha -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-gamma -dependent. Immunopathology induced by intimin enables the bacteria to promote conditions that are favorable for increased microbial colonization.

1 Department of Paediatric Gastroenterology, St. Bartholomews and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK.
2 Department of Biochemistry, Imperial College of Science, Technology, and Medicine, London SW7 2AZ, UK.
3 School of Biological Sciences, Division of Food Sciences, University of Nottingham, LE12 5RD, UK.

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