This project will examine the pathogenesis of L. braziliensis infection in affected patients and the hamster experimental model. The experiments are based on observations on disease expression in previous longitudinal studies in humans and experimentally infected hamsters. The potential role of immunologically mediated responses to outcome of L. braziliensis infection in patients whose clinical phenotype is analogous to the healer and non-healer phenotypes defined in experimental systems using inbred mice infected with L. major and L. donovani will be analyzed by three approaches: 1. the lymphocytes expanded and antibodies produced in individuals who have experienced inapparent or rapidly self-healing infection and those who have had chronic, or recurrent disease will be utilized to, a) identify the corresponding antigens in two dimensional (2- D) molecular profiles, and b) to determine the lymphokine mediator repertoires elicited in vitro; 2. biopsies of Montenegro reaction sites and in some cases active lesions of these same patient groups will be characterized with respect to the in situ response to L. braziliensis antigen, and lymphocytes will be cultured and expanded from these tissues to probe 2-D molecular profiles; 3. IgE and atopy will be evaluated in patients with mucosal and cutaneous disease and matched controls as a possible marker or risk factor for mucosal involvement. In parallel with the studies in humans, the effects of distinctive hypersensitivity responses and biological and chemical modulators of these responses will be tested in the hamster model of L. braziliensis infection. Metastasis has been found to be a reproducible behavior and will be exploited as a biological index of pathogenesis. Latent persistence of Leishmania after healing of lesions has been achieved either spontaneously of chemotherapeutically, will also be evaluated in this model. Quantitative methods will be utilized to assess the dissemination of parasites within lesions, lymphoid organs and apparently unaffected skin.
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