Modulation of human basophil function by schistosomiasis. (360G-Wellcome-080476_Z_06_Z)

IgE is key to both anti-helminth immunity and allergic hypersensitivities. Although cell-bound allergen-specific IgE mediates many allergy symptoms, highlevels of circulating IgE and FceR-bearing cells found in chronic helminth infections do not cause systemic clinical effects, even when infected individuals are exposed to intravenous allergen challenge, as when schistosomes are drug-killed in situ. We propose that examination of human basophil behaviour/biology in the context of chronic intravenous helminthiasiswill provide new insights into the pathophysiology and immunology of both helminth infections and allergic diseases. We focus on basophils because [a] they are key cells in allergic inflammation; [b] basophils can be readily accessed in human blood; [c] we have evidence that basophils are in a partially suppressed/controlled state in human schistosomiasis, which changes with chemotherapy. Preliminary data shows that we can successfully numerically, phenotypically and functionally study basophils from individuals in schistosomiasis endemic areas, in relation to parasitological and serological parameters. In schistosome-infected Kenyans, by systematically relating basophil function (differentially-regulated histamine, leucotriene C4, and IL-4 release) in the presence and absence of plasma, to changes in basophil phenotype numbers and circulating factors, we will identify suppressor/control mechanisms important for both anti-parasite immune responses and severity of allergic hypersensitivities. We will also investigate the modulating roles of 'infection' plasma factors in passively sensitizing/blocking normal basophil function.