The regulation of eosinophil production is not well understood. The long-term objective of the proposed research is to define the regulatory mechanisms involved in the stimulation of eosinophilopoiesis during parasitic infection. Eosinophils are thought to play a role in defense against parasites, but may also contribute to tissue damage in the host. Although certain eosinophil responses depend upon T lymphocytes, mechanisms of stimulated production of eosinophils have not been elucidated. The specific goals of the proposed research are to determine the cellular mechanisms of parasite-induced eosinophilia, to investigate the responsiveness of eosinophil progenitor cells to regulatory factors, and to determine if parasite antigens play a role in stimulating eosinophilopoiesis during infection with Toxocara canis. Toxocariasis is a parasitic disease of considerable public health significance primarily affecting children after ingestion of soil contaminated with infective eggs. Larval migration results in persistent eosinophilia and tissue granulomata. An ocular form of the disease may clinically mimic other serious ocular diseases, such as retinoblastoma. The proposed study will investigate eosinophilopoiesis by assaying eosinophil progenitor cells (CFU-EO) during the course of Toxocara infection. The responsiveness of CFU-EO to specific parasite antigens and to factors produced by accessory cells will.be studied using the in vitro assay. Elucidation of the mechanisms which regulate eosinophilopoiesis in parasitic infection should provide a basis for understanding other disorders in which eosinophil production is altered.
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