The goal of this grant proposal is to determine the role of eosinophils in the innate and adaptive immune response of mice to the nematode parasite Strongyloides stercoralis. In previous studies we have shown that protective immunity to this parasite is dependent on IL-5 and on eosinophils. This grant proposal will use a variety of methods to describe the mechanism of cosinophil involvement in immunity including: (1) the use of cytokine and eosinophil granule product transgenic (TG) and knockout mice (KO) mice (2) the use of combinatorial genetics with the TG and KO mice and (3) the testing and quantifying of the role of murine eosinophil granule products in the innate and the adaptive immune response. The specific goals of this project are: (1) To determine the role of eosinophils in killing larval S. stercoralis by the innate immune response. In this section we will determine if killing of larval S. stercoralis by the innate immune response is dependent on granule release from the eosinophils in the immediate environment of the larvae and which specific mouse eosinophil granule products are capable of killing larvae in vitro and in vivo. (2) To determine the role of eosinophils in the induction of the adaptive immune response to larval S. stercoralis. Three roles for eosinophils in the induction of the immune response will be evaluated, cytotoxic cells capable of killing and lysing the larvae antigen presenting cells and cytokine producing cells. (3) To determine the role of eosinophils in killing parasites through the adaptive immune response. In this final section we will determine how eosinophils participate in killing larvae in collaboration with IgM and complement. In conclusion, in this proposed study we will determine how eosinophils contribute in the protective immune response to S. stercoralis and in addition we will determine the role of these cells in the transition from the innate to the adaptive immune response to this infection.
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