Host-parasite interaction as a model to define immunological regulatory pathways.

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There is often the misconception that parasitic diseases are restricted to tropical regions of the world. This is far from the truth. The effects of parasitism are felt in Canada, where livestock, companion animals and humans can suffer from parasitic infections at the cost of millions of dollars annually. In this project we make use of a convenient laboratory model system - that of mice infected with the rat tapeworm, Hymenolepis diminuta - to ask a series of basic questions that address fundamental issues relating to the immune response directed at helminth (i.e. worm) parasites and how this knowledge can be used to both combat infection with helminth parasites, modualte mucosal immunity and affect co-morbidities. Three strands of investigation are woven into a unified research plan that assesses the two principal means by which helminth parasites can affect host immunity. First, a series of immunological studies will define the early (i.e. 1-5 days) changes in immune cell populations in mice that accompany infection with H. diminuta and then determine which of these drive the adaptive immune response responsible for expulsion of the worm. Second, focusing, on one immune signal, namely interleukin (IL)-10, we will determine the role for this molecule in (i) rejection of the parasite, (ii) recovery of the immune system after the mobilization of a spectrum of anti-worm events, and (iii) the ability to exert a bystander effect and suppress disease-related inflammation in the gut or joints. Third, a molecular analysis will seek to isolate and characterize bio-active molecules from the worm that may serve as blueprints for the development of novel immuno-suppressive drugs. As an integrated program, this study will provide fundamental data on immunological aspects of host-parasite (i.e. helminth) interactions that can be applied to the development of better anti-worm treatments and the development of strategies to manipulate the mammalian immune response.