The goals of this project are to define the immunologic mechanisms responsible for resistance to filarial infection, for the acquisition of filarial disease, and for the pathological reactions that develop in patients being treated for these infections. Differential immune responsiveness to filarial antigen among groups of individuals from areas endemic for bancroftian filariasis (Cook Islands, India) has shown generalized enhanced immunologic responsiveness in 'putatively immune' individuals. Screening of antibody responses identified at 43 kD larval antigen differentially recognized by the immune group; this antigen has been subsequently isolated from a W. bancrofti DNA expression library, the gene cloned, and the molecule identified as filarial chitinase (now a vaccine candidate). A 17 year follow-up study in the Cook Islands provided the opportunity to identify long-term effects of prenatal exposure to maternal filarial infection on subsequent immune responsiveness to filarial antigens. Studies of lymphocyte and antibody responses of children born 17 - 19 years previously to mothers diagnosed at that time as either microfilaremic or amicrofilaremic showed that children of infection-free mothers (i.e., those with no prenatal exposure to filarial antigen) had significantly greater responses to microfilarial antigen than did children born to microfilaremic mothers. Prenatal 'tolerization' is the most likely explanation for this finding. Following treatment of filarial infections, there is often an acute inflammatory reaction and a post-treatment eosinophilia. The eosinophilia has been shown to depend on the cytokine IL-5 probably released from peripheral blood T cells. This severe clinical reaction (Mazzotti reaction) has now been linked to inflammatory pathways characterized by the presence of IL-6 and TNF-alpha in the blood of affected patients.
