The tapeworm Hymenolepis diminuta is a model for the impact of helminth colonization on the mammalian immune system and a candidate therapeutic agent for immune mediated inflammatory diseases (IMIDs). In mice, H. diminuta protects against models of inflammatory colitis by inducing a strong type 2 immune response that is activated to expel the immature worm. Rats are the definitive host of H. diminuta, and are colonized stably and over long time periods without harming the host. Rats mount a mild type 2 immune response to H. diminuta colonization, but this response does not generally ameliorate colitis. Here we investigate the ability of different life cycle stages of H. diminuta to protect rats against a model of colitis induced through application of the haptenizing agent dinitrobenzene sulphonic acid (DNBS) directly to the colon, and monitor rat clinical health, systemic inflammation measured by TNFα and IL-1β, and the gut microbiota. We show that immature H. diminuta induces a type 2 response as measured by increased IL-4, IL-13 and IL-10 expression, but does not protect against colitis. In contrast, rats colonized with mature H. diminuta and challenged with severe colitis (two applications of DNBS) have lower inflammation and less severe clinical symptoms. This effect is not related the initial type 2 immune response. The gut microbiota is disrupted during colitis and does not appear to play an overt role in H. diminuta-mediated protection.
Keywords: Benign helminth; DNBS colitis; Hymenolepis diminuta; IL-10 cytokines; TNFα; gut microbiota; helminth therapy.