H HEPATICUS--PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

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DESCRIPTION (Adapted from the applicant's abstract): The human inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are multifactorial disorders whose etiology remains unknown. Animal models have been developed to help understand the complex interaction between the immune system and intestinal antigens - particularly bacteria - which appear to be involved in the pathogenesis of disease. Infection with the mouse pathogen Helicobacter hepaticus has been associated with disease in mice which are genetically and/or immunologically predisposed to the development of IBD. H. hepaticus, like the human gastroduodenal pathogen H. pylori, expresses putative virulence factors which may contribute to chronic mucosal inflammation, epithelial cell proliferation, and an increased risk for cancer. The investigators propose to test the hypothesis that infection with H. hepaticus is sufficient for expression of disease in mice which are predisposed to the development of IBD. They also propose to identify the bacterial virulence factors of H. hepaticus which are involved in the pathogenesis of IBD in the mouse models. These studies will characterize the mechanism by which infection with a single bacterial species can affect expression of disease in mouse models of IBD. It is hoped that these studies will lead to the development of rational therapy for patients suffering from Crohn's disease and ulcerative colitis.