Schistosomiasis, hookworm and atopy in Uganda: IgE function, regulation and immunity. (360G-Wellcome-083931_Z_07_A)

Key goals: Two schistosomiasis/hookworm treatment-reinfection studies in cohorts exposed to both infections, with detailed GIS and exposure analysis to give precise immunity estimates, and associations between infections controlled for overlapping transmission clustering. Study 1: compare first and second treatments for post-treatment immunological changes, and responses to in vivo Ag released from killed worms, for evidence of specific and non-specific cross regulation, affecting reinfection immunity. Specifically, measure: Schistosome, hookworm and aeroallergen IgE responses; Specific IgE function in passive histamine-release with Ag stimulation; Number/phenotype of circulating basophils and eosinophils, and tissue mast cell activity. Study 2: repeat most informative Study 1 assays, in relation to cellular responses: Whole-blood cytokine responses to schistosome and hookworm Ags; Active histamine-release from whole-blood samples stimulated native & recombinant schistosome, hookworm, aeroallergens; IL-10 and TGF-beta effects on in vitro cytokines induced by schistosome and hookworm; Skin-prick reactivity to aeroallergens; Identify cellular sources of IgE/IgE-effector modulatory molecules. Test hypothesis that: (a).Eosinophils have a regulatory role; in turn affected by immune modulators; non-responsive eosinophils are associated with reinfection susceptibility, (b).Susceptibility to schistosomiasis and hookworm is linked, via mechanisms that also affectallergy. (c).Life-stage expression and molecular structure of schistosome allergen-like Ags influence IgE and IgE-effector function triggering.