Immediate Hypersensitivity Responses--Helminth Infection

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Abstract

Hypereosinophilic conditions have been studied extensively, and we have identified new markers that distinguish between several important variants of this syndrome. We have instituted new therapies (imatinib, anti-IL5) for the treatment of each of these variants. The interaction between helminth infeciton and allergic disease has been studied using epidemiological tools coupled with physiological measurements of allergic disease and immunological assessments. We have demonstrated that chronic helminth infection protects against allergic diseases. Production of IL-10 could provide a link between the antigen-induced increases in IL-4 production, the modulation of the T cell response, and the production of IgG4 in chronic filarial infection. Studies done to date have demonstrated the CD4+ cells (and neither the monocytes nor the basophils) are the overwhelmingly major source of IL-10 in chronic filarial infection. Using infective stage larvare (L3) and Langerhans' cell obtained from skin blisters, we have found that the parasites, by themselves, have an activity that promotes eosinophil chemotaxis. This activity appears to act through G-coupled receptors on human eosinophils and utilizes (in part) CCR3. Moreover, the eosinophils actively take up the secreted parasite antigens (as assessed by confocal microscopy) although their subcellular localization has not been determined. Using antigens from each of the major stages (microfilarial, infective larval, adult females, adult males) and using live parasites from each stage, we have been unable to induce histamine release (or IL-4 production) by human basophils in the absence of basophil sensitization with parsasite-specific IgE.