Original Article
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 21, 2014; 20(7): 1797-1806
Published online Feb 21, 2014. doi: 10.3748/wjg.v20.i7.1797
Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-/- mice
Ekta K Bhardwaj, Kathryn J Else, Michael T Rogan, Geoffrey Warhurst
Ekta K Bhardwaj, Michael T Rogan, Geoffrey Warhurst, School of Environment and Life Sciences, University of Salford, Salford M68HD, United Kingdom
Kathryn J Else, Faculty of Life Sciences, University of Manchester, Manchester M139PT, United Kingdom
Geoffrey Warhurst, Infection, Injury and Inflammation Research Group, Salford Royal NHS Foundation Trust, Salford M68HD, United Kingdom
Author contributions: Bhardwaj EK contributed to the study design, data acquisition and analysis and to data interpretation and manuscript drafting and revision; Else KJ, Rogan MT and Warhurst G contributed to study design, data interpretation and manuscript drafting and revision; all authors gave final approval to the final version of the article.
Correspondence to: Geoffrey Warhurst, PhD, Infection, Injury and Inflammation Research Group, Salford Royal NHS Foundation Trust, Clinical Sciences Building, Salford M68HD, United Kingdom. geoffrey.warhurst@manchester.ac.uk
Telephone: +44-161-2064403
Received: August 27, 2013
Revised: October 17, 2013
Accepted: November 18, 2013
Published online: February 21, 2014
Processing time: 196 Days and 11.8 Hours
Abstract

AIM: To investigate the influence of Trichuris muris (T. muris) infection in a mouse model of genetic susceptibility to inflammatory bowel disease, Mdr1a-/-.

METHODS: Mdr1a-/- mice were housed under specific pathogen free conditions to slow the development of colitis and compared to congenic FVB controls. Mice were infected with approximately 200 embryonated ova from T. muris and assessed for worm burden and histological and functional markers of gut inflammation on day 19 post infection.

RESULTS: Mdr1a-/- mice exhibited a marked increase in susceptibility to T. muris infection with a 10-fold increase in colonic worm count by day 19 pi compared to FVB controls. Prior to infection, Mdr1a-/- exhibited low-level mucosal inflammation with evidence of an enhanced Th1 environment. T. muris infection accelerated the progression of colitis in Mdr1a-/- as evidenced by marked increases in several indicators including histological damage score, mucosal CD4+ T-cell and DC infiltration and dramatically increased production of pro-inflammatory cytokines.

CONCLUSION: These data provide further evidence of the complex interaction between T. muris and an inflammatory bowel disease (IBD)-susceptible host which may have relevance to the application of helminth therapy in the treatment of human IBD.

Keywords: Helminth; Colitis; Inflammatory bowel disease; P-glycoprotein; Mdr1a

Core tip: This study investigates the interaction between the helminth parasite Trichuris muris (T. muris) and Mdr1a-/- mice, a genetic model of inflammatory bowel disease linked to deficiency of a key transporter protein in the gut barrier. The main findings are that (1) Mdr1a mice exhibit dramatically increased susceptibility to worm infection compared to congenic controls and (2) challenge with T. muris induces severe pathological changes consistent with a marked exacerbation of colitis in this model with preliminary evidence pointing to worm persistence as a driver of this effect. These findings will be of interest in the emerging field of helminth therapy in inflammatory bowel disease (IBD) providing further evidence of the complexity of worm interaction with an IBD-susceptible host.