Host parasite interaction in a mouse model of inflammatory bowel disease

Bhardwaj, EK 2012, Host parasite interaction in a mouse model of inflammatory bowel disease , PhD thesis, University of Salford.

PDF Restricted to Repository staff only until 31 July 2024. Download (15MB) | Request a copy

Abstract

Prevalence of inflammatory bowel disease (IBD) is far more common in developed countries as compared to the developing world, where infection with intestinal parasites is common. The hygiene hypothesis suggests lack of infection predisposes to the development of IBD in genetically susceptible people. However, little is known immunologically about how gut parasites alter IBD progression. We have used mdrla KO mice on an FVB background to investigate any change in progression of colitis in mice infected with Trichuris muris. Pglycoprotein (PGP), present in the apical membrane of gut epithelial cells, is encoded by the mdrla gene. This protein inhibits absorption of many drugs and acts as a transport protein. Mice which lack the mdrla gene (mdrla KO) develop spontaneous colitis in the presence of enteric bacteria. In the current study we attempted to address the following questions: (1) Does host susceptibility to IBD affect the susceptibility to helminth (T.muris} infection? (2) Does helminth infection have an effect on progression of colitis in hosts susceptible to colonic inflammation? (3) Does gut epithelial barrier dysfunction play a role in translocation of bacteria and the development of colitis? Our results reveal that mdrla KO mice have a more Th 1 type of gut environment and delayed worm expulsion compared to the wild type. In addition, we found that mice susceptible to colitis developed severe gut inflammation at an earlier age following T.muris infection. We also demonstrated that bacterial translocation did occur in the mdrla KO mice, though we failed to find any significant difference compared to the wild type. Together, these results suggest that the mice prone to colitis were also prone to Trichiuris infection and T.muris infection accelerated the progression of colitis in mice susceptible to colitis.

Item Type:	Thesis (PhD)
Contributors:	Rogan, MT (Supervisor)
Schools:	Schools > School of Environment and Life Sciences
Depositing User:	Institutional Repository
Date Deposited:	28 Jul 2021 10:35
Last Modified:	04 Aug 2022 11:23
URI:	https://usir.salford.ac.uk/id/eprint/61334

Actions (login required)

Edit record (repository staff only)