The role of mast cells for directing T cell-dependent immunity in cutaneous leishmaniasis

利什曼病是一种寄生虫病，全世界约有1200万感染者。我们以前已经表明，MC也参与控制寄生虫利什曼原虫感染。皮内接种生理相关的低剂量L。主要导致局部MC活化，用DT处理以删除MC的遗传MC缺陷型KitwIKitw-v、KitW-sh/KitW-sh以及Mcpt 5xiDTR小鼠显示出显著恶化的疾病，具有较大的皮肤损伤。此外，MC缺乏与较高的病变寄生虫负荷，增强内脏化和主要的有害的Th 2/Th 17/Treg免疫反应。我们现在打算通过分析MC对抗原呈递和T细胞教育的直接贡献来研究作用机制。此外，我们将评估MC衍生因子的作用和MC与抗原呈递细胞（如树突状细胞）和/或T细胞在体内的相互作用，使用复杂的小鼠模型，涉及骨髓嵌合体结合MC和DC缺陷和/或选择性缺失，如MHC II类，CD 40 L或细胞因子从MC。从长远来看，MC功能的调节可能会改变这种重要的人类病原体感染的疾病结局。

Leishmaniasis is a parasitic disease with ~12 million infected people worldwide. We have previously shown that MC are also involved in the control of infections with the parasite Leishmania major. Intradermal inoculation of physiologically relevant low doses of L. major resulted in local MC activation and genetically MC-deficient KitwIKitw-v, KitW-sh/KitW-sh as well as Mcpt5xiDTR mice treated with DT to delete MC displayed significantly worsened disease with larger skin lesions. In addition, MC deficiency was associated with higher lesional parasite burdens, enhanced visceralization and predominant detrimental Th2/Th17/Treg immune responses. We now intend to study the mechanism of action by analysing the direct contribution of MC to antigen presentation and T cell education. In addition, we will assess the role of MCderived factors and the interaction of MC with antigen presenting cells (e.g. dendritic cells) and/or T cells in vivo using sophisticated mouse models involving bone marrow chimeras combining MC and DC deficiency and/or selective deletion of e.g. MHC class II, CD40L or cytokines from MC. In the long run, modulation of MC function may allow for a modification of disease outcome in infections with this important human pathogen.