Innate immunity in leishmaniasis

利什曼原虫在埃塞俄比亚引起毁容和危及生命的疾病。该疾病的一个典型特征是强烈两极化的临床过程，即皮肤利什曼病的局部（LCL）和播散（DCL）形式以及内脏利什曼病（VL）。皮肤和内脏利什曼病都是埃塞俄比亚的地方病。与适应性免疫反应的深入研究相反，关于利什曼原虫的先天免疫反应的知识令人惊讶地稀少。然而，由于先天免疫反应不仅对于有效的早期防御至关重要，而且还影响适应性免疫反应的发展，因此了解病原体诱导的先天免疫功能障碍对于对抗该疾病和制定免疫干预策略至关重要。由于利什曼原虫感染不会导致全身免疫缺陷或免疫低反应性，我们假设利什曼原虫只靶向那些对寄生虫的存活有害的先天免疫功能。第一个供资期的研究目标是确定这些目标职能。我们希望确定寄生虫诱导的中性粒细胞，NK细胞，巨噬细胞前体细胞和树突状细胞（DC）亚型的功能障碍，这些功能障碍与疾病的类型和严重程度相关。该项目将由埃塞俄比亚和德国科学家通过分享基础知识和专业知识进行合作。该合作将加强埃塞俄比亚的能力建设，并将为德国科学家开展热带医学和人类免疫学研究提供极好的机会。

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.