title: Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-/- mice.
abstract: OBJECTIVE
  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 CD⁺ T-cell and DC infiltration and dramatically increased production of pro-inflammatory cytokines.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ekta K Bhardwaj, Michael T Rogan, Geoffrey Warhurst, School of Environment and Life Sciences, University of Salford, Salford M68HD, United Kingdom.
authors.forename: Ekta K
authors.initials: EK
authors.lastname: Bhardwaj
authors.affiliation: Ekta K Bhardwaj, Michael T Rogan, Geoffrey Warhurst, School of Environment and Life Sciences, University of Salford, Salford M68HD, United Kingdom.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
authors.affiliation: Ekta K Bhardwaj, Michael T Rogan, Geoffrey Warhurst, School of Environment and Life Sciences, University of Salford, Salford M68HD, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rogan
authors.affiliation: Ekta K Bhardwaj, Michael T Rogan, Geoffrey Warhurst, School of Environment and Life Sciences, University of Salford, Salford M68HD, United Kingdom.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Warhurst
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D003092:Colitis / Q000150:complications / Q000235:genetics* / Q000469:parasitology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000469:parasitology / Q000628:therapy; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D014257:Trichuriasis / Q000235:genetics*; D014258:Trichuris
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C095122:multidrug resistance protein 3
keywords: Colitis; Helminth; Inflammatory bowel disease; Mdr1a; P-glycoprotein