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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052413-02
Application #
2856818
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Hamilton, Frank A
Project Start
1998-01-01
Project End
2002-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Whary, Mark T; Muthupalani, Sureshkumar; Ge, Zhongming et al. (2014) Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota. Microbes Infect 16:345-55
Muthupalani, Sureshkumar; Ge, Zhongming; Feng, Yan et al. (2012) Systemic macrophage depletion inhibits Helicobacter bilis-induced proinflammatory cytokine-mediated typhlocolitis and impairs bacterial colonization dynamics in a BALB/c Rag2-/- mouse model of inflammatory bowel disease. Infect Immun 80:4388-97
Lofgren, Jennifer Ls; Esmail, Michael; Mobley, Melissa et al. (2012) Prevalence of murine Helicobacter spp. Infection is reduced by restocking research colonies with Helicobacter-free mice. J Am Assoc Lab Anim Sci 51:436-42
Turk, Michelle L; Cacioppo, Laura D; Ge, Zhongming et al. (2012) Persistent Helicobacter pullorum colonization in C57BL/6NTac mice: a new mouse model for an emerging zoonosis. J Med Microbiol 61:720-8
Charoenlap, Nisanart; Shen, Zeli; McBee, Megan E et al. (2012) Alkyl hydroperoxide reductase is required for Helicobacter cinaedi intestinal colonization and survival under oxidative stress in BALB/c and BALB/c interleukin-10-/- mice. Infect Immun 80:921-8
Beisele, Maike; Shen, Zeli; Parry, Nicola et al. (2011) Helicobacter marmotae and novel Helicobacter and Campylobacter species isolated from the livers and intestines of prairie dogs. J Med Microbiol 60:1366-74
Fox, J G; Ge, Z; Whary, M T et al. (2011) Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer. Mucosal Immunol 4:22-30
GarcĂ­a, Alexis; Zeng, Yu; Muthupalani, Sureshkumar et al. (2011) Helicobacter hepaticus--induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response. Cancer Res 71:2529-40
Whary, Mark T; Taylor, Nancy S; Feng, Yan et al. (2011) Lactobacillus reuteri promotes Helicobacter hepaticus-associated typhlocolitis in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice. Immunology 133:165-78
Boutin, S R; Shen, Z; Roesch, P L et al. (2010) Helicobacter pullorum outbreak in C57BL/6NTac and C3H/HeNTac barrier-maintained mice. J Clin Microbiol 48:1908-10

Showing the most recent 10 out of 47 publications