IMMUNOREGULATION IN HUMAN STRONGYLOIDIASIS

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DESCRIPTION (provided by applicant): Strongyloidiasis is a significant medical problem in Peru. Although strongyloidiasis symptoms may be mild in immunocompetent hosts, it may present as a severe disseminated form in immunocompromised individuals (Strongyloides hyperinfection). In Peru we are increasingly observing Strongyloides hyperinfection, especially in persons co-infected with the Human T-cell-lymphotropic virus 1 (HTLV-1). Interestingly, Strongyloides hyperinfection rarely presents in persons with advanced HIV/AIDS. The immunological processes leading to these different disease manifestations are not completely understood. In our preliminary data, we made the novel observation that Strongyloides/HTLV-1 co-infected patients failed to produce IL-5 in response to Strongyloides larval antigens. Based on these data, we hypothesize that the Th1 or regulatory responses noted with HTLV-1 interfere with the Th2 responses preventing hyperinfection. The specific aims are: 1) to test the hypothesis that suppressed immune responses to specific Strongyloides larval antigens in HTLV-1 infected patients with strongyloidiasis correlate with a higher number of circulating Th1, T-regulatory cells and/or regulatory cytokines when compared to normal subjects with strongyloidiasis, 2) To test the hypothesis that the low rate of Strongyloides hyperinfection in HIV patients is due to a preserved specific Th2 type response to Strongyloides larval antigen; and 3) to characterize the clinical presentation and immune responses to Strongyloides larval antigen in patients with dual HIV/HTLV-1 infection to test the hypothesis that HTLV-1 enhances the immunosuppressive effects of HIV. We will accomplish these goals by prospectively studying cytokine responses to Strongyloides larval antigen. We will further characterize cells responsible for cytokine production by flow cytometry. In accomplishing these studies, we will advance knowledge of the immunoregulatory effects of human retroviral infections. We will better understand the clinical and immunological responses to strongyloidiasis and set the basis for further studies focusing on immunity and vaccine development. Studies of immunoregulation in strongyloidiasis may also lead to insights needed for addressing the burden of intestinal nematodes, which affect billions of people.