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ELICITING AN IMMUNE MEMORY RESPONSE TO H. DIMINUTA AS A MEANS TO TREAT MURINE COLITIS EVOKED BY DINITROBENZENE SULPHONIC ACID (DNBS)
C Beaurepaire, MM Hunter, A Wang, DM McKay
Gastrointestinal Research Group, University of Calgary
Investigations using a variety of species of helminth parasites have shown that infection with these organisms can alleviate a spectrum of diseases, including intestinal inflammation. We have shown that infection of mice with the tapeworm parasite Hymenolepis diminuta prior to, and after, challenge with DNBS results in significantly less severe colitis. Mice given a secondary challenge of H. diminuta respond quickly to the infection and reject the worms within 2-3 day of infection, indicating that the mice have developed immunological memory to H. diminuta. Seeking to exploit this response, we assessed if secondary H. diminuta infection mice would reduced DNBS-induced colitis.
METHODS: Mice were orally gavaged with 5 H. diminuta cysticercoids and 28 days later some mice received a second oral infection or were injected ip. with a crude cysticercoid antigen extract and DNBS (3mg in 50% EtOH) was delivered intra-rectally. Controls consisted of: naïve mice, DNBS only and mice infected 28 day prior to DNBS (i.e. no secondary challenge). Three days after DNBS treatment a clinical disease score was calculated, the mice were sacrificed, blood collected for eosinophil counts, colonic histology and MPO levels assessed.
RESULTS: As expected DNBS treated mice displayed cardinal signs of colitis and these were not significantly different from those observed in mice given a single H. diminuta infection 8 days previously. However, mice that received a secondary worm challenge fared significantly better than DNBS only-treated mice as gauged by clinical scores (DNBS: 2.68, DNBS+ H.d.: 1.28, n=14), colonic MPO levels (DNBS: 3.54±1.80, DNBS+H.d.:1.79±1.07, n=5), weight loss and colon length measurements (DNBS: 7.83 cm ± 1.11 cm, DNBS+H.d. : 8.81 cm± 1.48 cm, n=13) .
SUMMARY: A secondary challenge of H. diminuta in sensitized mice reduces the colitis associated with concomitant delivery of DNBS. Identification of the antigen(s) that triggers the protective event, would allow the development of a helminth-based anti-inflammatory therapy that would not require subsequent viable worm infections.
Funded by CCFC