Role and therapeutic potential of different skin and lymph node-resident dendritic cell subsets to control cutaneous leishmaniasis in mice

皮肤利什曼病是世界上最常见的传染病之一。尽管做出了许多努力，但目前还没有疫苗。本项目的主要目标是详细描述皮肤树突状细胞（DC）亚群在利什曼病中的作用。从我们之前的实验中可以清楚地看出，皮肤中不同的DC亚群在T细胞启动和教育过程中发挥不同的作用，这与实验小鼠利什曼病的不同疾病结果直接相关。在项目的前3年，我们证明了表皮朗格汉斯细胞（LC）通过诱导促进寄生虫持久性的调节性T细胞（Treg）来调节抗利什曼原虫免疫。这很可能是由于IL-10水平的增加。另一方面，对其他皮肤DC亚群进行条件细胞消融的初步实验显示，皮肤DC对L. major感染具有保护作用。因此，在目前的项目中，我们的目标是(i)进一步表征DC亚群介导的保护，（ii）确定DC亚群如何教育不同T细胞亚型的分子机制，以及（iii）研究不同皮肤DC亚群之间激活信号的差异是否允许根据疫苗开发选择靶向方法。

Cutaneous leishmaniasis is one of the most frequent infectious diseases worldwide. Despite many efforts, a vaccine is not available yet. The main goal of the present project is a detailed characterization of the role of skin dendritic cell (DC) subsets in leishmaniasis. From our prior experiments, it became clear that different DC subsets in the skin play divergent roles during T cell priming and education, which is directly linked to different disease outcomes in experimental murine leishmaniasis. During the first 3 years of the project, we demonstrated that epidermal Langerhans cells (LC) regulate anti-Leishmania immunity by inducing regulatory T cells (Treg) that promote parasite persistence. This is most likely due to increased levels of IL-10. On the other hand, initial experiments using conditional cell ablation of other skin DC subsets revealed a protective role of dermal DC against L. major infection. Thus, in the present project we aim to (i) further characterize the DC subset mediating protection, (ii) determine the molecular mechanism how the DC subsets educate different T cell subtypes, and (iii) study if differences in the activation signal between the various skin DC subsets allow for selective targeting approaches in light of vaccine development.