Infection with the tapeworm parasite <i>Hymenolepis diminuta</i> in early life protects against experimental colitis in mice

Background The hygiene hypothesis asserts that lack of exposure to infectious disease in childhood contributes to the development of auto‐inflammatory disease. We showed that infection with the rat tapeworm Hymenolepis diminuta evoked a Th2 response, including IL‐10, in adult mice and protected the mice from di‐nitrobenzene‐sulfonic acid (DNBS) induced colitis. Within North America there has been a startling increase in pediatric (early)‐onset inflammatory bowel disease. We tested the hypothesis that infection of mice immediately post‐weaning with H. diminuta would protect them from colitis. Aim To determine if three‐week old mice effectively expel H. diminuta and receive protection from chemically‐induced colitis by infection with this helminth parasite. Methods First, helminth infectivity was compared in three‐ and eight‐week old Balb/c mice (bred at Univ. Calgary). Second, three‐week old Balb/c mice were infected with 5 cysticercoids of H. diminuta by oral gavage and 8 or 10 days later received 1.5 mg of DNBS intra‐rectally. Colitis was assessed 72h post‐DNBS by: 1) loss of body weight, 2) colon length, 3) disease activity score, 4) histopathology, and 5) concanavalin‐A stimulated cytokine production from spleen cells. Third, the ability of re‐challenge with H. diminuta antigen to protect mice from DNBS‐induced colitis in later life was tested. Results Juvenile mice expelled H. diminuta although this was delayed by ~2–3 days compared to infected adult mice. Mice infected with H. diminuta 8 days DNBS were not protected against colitis, whereas those infected 10‐days prior to ir. DNBS displayed substantially severe colitis The anti‐colitic effect in the infected mice was paralleled by increased splenic production of IL‐4 and IL‐10, and increased mRNA IL‐4, IL‐10 and FOXP3 mRNA in extracts of colon. Infection also lead to immunological memory in the young mice allowing triggering of an anti‐colitic effect by systemic delivery of worm antigen to previously infected mice. Conclusions Juvenile mice expel H. diminuta (indicating a functional immune response) and infected mice can be protected from DNBS‐induced colitis. We provide these preliminary data in support of the consideration of helminth therapy in early‐onset of IBD and speculate that exploiting immunological memory for H. diminuta could be a new an Support or Funding Information Supported by Yamanashi Scholarship and NSERC CREATE Host‐Parasite Interactions scholarship to TA and NSERC operating grant to DMM.

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