A90 EARLY LIFE INFECTION OF MICE WITH THE TAPEWORM PARASITE HYMENOLEPIS DIMINUTA PROTECTS AGAINST DNBS-INDUCED COLITIS

Abstract

Background

According to the hygiene hypothesis, the lack of exposure to intestinal helminths in childhood could be an important environmental factor in the development of auto-inflammatory disease. In Canada there has been a significant increase in pediatric (early) and adult (later) onset IBD. We showed that infection with H. diminuta reduced the severity of di-nitrobenzene sulphonic acid (DNBS) in adult mice. Here we test the hypothesis that infection with this helminth will exert an anti-inflammatory benefit in young mice.

Aims

To define if three-week old (young) mice can expel H. diminuta and if they are protected from DNBS-induced colitis.

Methods

First, helminth infectivity was compared in three- and eight-week old Balb/c mice (bred at Univ. Calgary). Second, young mice were orally infected with 5 cysticercoids of H. diminuta 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. In other experiments, the ability of re-challenge with helminth antigen to protect mice from DNBS-induced colitis in later life was tested.

Results

The young mice successfully rejected H. diminuta, although this was slightly delayed by ~3 days compared to adult mice. The young mice developed DNBS-colitis as determined by all indicates of measurement. Mice infected with H. diminuta 8 days before administration of DNBS showed no amelioration of disease; however, adjusting the temporal aspect of the study, we found that mice infected 10 days prior to DNBS had substantially less severe colitis (this 10 day time-point corresponded with expulsion of the parasite). Furthermore, helminth antigen treatment after early life infection protected the mice from colitis in later life.

Conclusions

Young mice expel H. diminuta by a functional immune response and infected mice can be protected from DNBS-induced colitis. While the mechanism of the anti-colitic effect is likely to parallel that seen in adults (i.e. involves IL-4, IL-10 and IgG1). H. diminuta antigen treatment after early life infection protects against colitis in later life. We present these preliminary data in support of the consideration of helminth therapy in early onset IBD, and triggering of anti-helminth immunological memory to treat IBD later in life.

Funding Agencies

Yamanashi Scholarship, NSERC CREATE Host-Parasite Interaction