CUTANEOUS DETERMINANTS OF RESISTANCE TO LEISHMANIA

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The objective of these studies is to evaluate the role of the cutaneous accessory cells in host resistance to leishmaniasis. These macrophage-like cells form an anastomosing network of antigen-presenting cells in skin, the body's first line of defense against agents of Leishmaniasis. Preliminary studies have shown that antigen-presenting macrophages in epidermal cell suspensions selectively take up Leishmania parasites to which the host can mount an effective immune response. The first phase of the project will examine the ability of cutaneous accessory cells, collected from normal and infected mouse skin, to present parasite antigen to T-cells in vitro. Results will be extended to a murine in vivo model to investigate the role of cutaneous accessory cells in the induction of protective immunity to cutaneous leishmaniasis. In the second phase, accessory cell function will be selectively inactivated and the effect of this treatment on parasite antigen presentation in vitro and on the resolution of cutaneous leishmaniasis in vivo will be evaluated. The third phase will evaluate the ability of cutaneous accessory cells, normally bypassed during infection by intravascular inoculation, to process and present antigen from the agent of visceral leishmaniasis, a parasite to which the host develops little or no immunity when infected. Results from these experiments will be applicable to the understanding of pathogenesis in leishmaniasis, and to the development of effective vaccines. Results may also contribute to our understanding of the role of cutaneous antigen-presenting cells in infectious diseases.