A77 TAPEWORM PARASITE HYMENOLEPIS DIMINUTA PROTECTS YOUNG MICE FROM EXPERIMENTAL COLITIS BY A RECALL MEMORY RESPONSE WITH WORM ANTIGEN

Lack of exposure to helminth parasites, as predicted by the hygiene hypothesis, would contribute to the development of auto-inflammatory disease. Previous studies revealed that infection with rat tapeworm, H. diminuta, reduced the severity of di-nitrobenzene sulphonic acid (DNBS)-induced colitis in adult mice. There has been a significant increase in pediatric onset IBD in Canada. Consequently the hypothesis that infection with this helminth would exert an anti-colitic benefit in young mice was tested. To determine if three-week old (young) mice can expel H. diminuta and are protected from DNBS-induced colitis, and if an anti-colitic response could be elicited by systemic antigen challenge of previously infected mice (i.e. evoking an immunological memory response). Three- and eight-week old (adult) Balb/c mice were orally infected with 5 cysticercoids of H. diminuta to assess infectivity and TH2 immunity. Young mice were infected with H. diminuta and 8 or 10 days later received 1.5 mg of DNBS intra-rectally. Colitis was assessed 72h post-DNBS by: 1) colon length, 2) disease activity score, 3) histopathology, and 4) concanavalin-A stimulated cytokine production from spleen cells. Finally, the ability of re-challenge with helminth antigen (HdE) after early life infection to protect mice from DNBS-induced colitis was tested. Young and adult mice evoked Th2 responses and successfully expelled H. diminuta, although worm expulsion was delayed by ~2 days in young mice compared to adults. The young mice developed DNBS-colitis as determined by all indicator of disease. Colitis was less severe in young mice infected 10 but not 8 days before DNBS-treatment, and was associated with an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected 28 days prior to DNBS were not protected, but injection of these mice the with (ip., 500 μg) resulted in less disease and boosted splenic output of IL-4 and IL-10. Immunological memory was confirmed by increased serum anti-H. diminuta IgG. Young mice rejected H. diminuta and were protected from DNBS-induced colitis. Exposure H. diminuta antigen treatment after early life infection protects against colitis in later life. We present these preliminary data in support of the putative value of helminth therapy in early onset IBD, and reveal that triggering of anti-helminth immunological memory can treat IBD later in life. Yamanashi Scholarship, NSERC CREATE Host-Parasite Interactions scholarship

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