Host parasite interaction in a mouse model of inflammatory bowel disease

Prevalence of inflammatory bowel disease (IBD) is far more common in developed countriesas 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 ingenetically susceptible people. However, little is known immunologically about how gutparasites alter IBD progression. We have used mdrla KO mice on an FVB background toinvestigate 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 themdrla 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 ofenteric 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 tocolonic inflammation? (3) Does gut epithelial barrier dysfunction play a role in translocationof bacteria and the development of colitis? Our results reveal that mdrla KO mice have amore Th 1 type of gut environment and delayed worm expulsion compared to the wild type. Inaddition, we found that mice susceptible to colitis developed severe gut inflammation at anearlier age following T.muris infection. We also demonstrated that bacterial translocation didoccur in the mdrla KO mice, though we failed to find any significant difference compared tothe wild type. Together, these results suggest that the mice prone to colitis were also prone toTrichiuris infection and T.muris infection accelerated the progression of colitis in micesusceptible to colitis.

Level dc:type.qualificationlevel

Doctoral (Level 8)

Year dc:date.issued

2012

Author dc:creator

• Bhardwaj, EK

Language dc:language

en

Identifier

oai:salford-repository.worktribe.com:1338245

OAI identifier oai:identifier

oai:salford-repository.worktribe.com:1338245