EK Bhardwaj
Host parasite interaction in a mouse model of inflammatory bowel disease
Bhardwaj, EK
Authors
Contributors
MT Rogan M.T.Rogan@salford.ac.uk
Supervisor
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.
Thesis Type | Thesis |
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Deposit Date | Jul 28, 2021 |
Award Date | Aug 1, 2012 |
This file is under embargo due to copyright reasons.
Contact Library-ThesesRequest@salford.ac.uk to request a copy for personal use.
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