Innate immunity in leishmaniasis

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Leishmania parasites cause disfiguring and life-threatening diseases in Ethiopia. A typical feature of the disease is the strongly polarized clinical course, i.e. the localized (LCL) and disseminated (DCL) forms of cutaneous leishmaniasis as well as the visceral leishmaniasis (VL). Both cutaneous and visceral leishmaniasis are endemic in Ethiopia. In contrast to the intensive research of adaptive immune responses, surprisingly sparse knowledge exists about the innate immune responses to Leishmania parasites. However, since innate immune responses are not only essential for effective early defence, but they shape the development of adaptive immune responses as well, understanding the pathogen-induced innate immune dysfunctions is essential to combat the disease and to develop immune intervention strategies.Since Leishmania infection does not lead to a general immune deficiency or immune hyporesponsiveness, we hypothesize that Leishmania parasites target only those innate immune functions which are detrimental for the survival of the parasites. The goal of the study in the first funding period will be to identify these target functions. We expect to identify parasite-induced dysfunctions of neutrophils, NK-cells, macrophage precursors, and dendritic cell (DC) subtypes which correlate with the type and severity of disease.The project will be carried in collaboration between Ethiopian and German scientists by sharing ground-base knowledge and expertise. The co-operation will strengthen capacitybuilding in Ethiopia and will provide excellent opportunities for German scientists to carry out research on tropical medicine and human immunology.