The role of bacteria-induced cell death in phagocytes for the development of the anti-bacterial immune response

这个项目的目的是了解细菌诱导的细胞死亡在发展生产性免疫反应中的作用。摄取细菌可诱导粒细胞和巨噬细胞的凋亡。树突状细胞(DC)在摄取凋亡细胞和将吞噬的抗原呈递给T细胞方面是有效的。由此，我们得出一个假设，吞噬诱导的原代吞噬细胞的凋亡被用来使细菌抗原可供DC和T细胞使用。这一概念将通过以下问题来研究：1.吞噬诱导的细胞死亡是如何调节的？2.细胞死亡的形式(由吞噬或其他刺激诱导)和Toll样受体信号如何影响DC、DC成熟细胞对凋亡细胞的摄取及其交叉呈递能力？3.体内吞噬细胞的凋亡对适应性免疫反应的结果起什么作用？这些问题将在转基因小鼠和受体非依赖性巨噬细胞刺激的模型中得到解决。实验系统将包括体外和体内DC和T细胞功能的研究。

The aim of this project is to understand the role of bacteria-induced cell death for the development of a productive immune response. Ingestion of bacteria induces apoptosis in granulocytes and macrophages. Dendritic cells (DC) are efficient in the uptake of apoptotic cells and in the presentation of phagocytosed antigen to T cells. From this, we derive the hypothesis that phagocytosis-induced apoptosis of the primary phagocyte is used to make bacterial antigen available to DC and consecutively to T-cells. This notion will here be investigated pursuing the following questions: 1. How is "phagocytosis-induced cell death" regulated? 2. How does the form of cell death (induced by phagocytosis or by other stimuli) and toll-like receptor signalling affect uptake of the apoptotic cell by a DC, DC maturation and its capacity for cross-presentation? 3. What is the role of apoptosis of phagocytes in vivo for the outcome of an adaptive immune response? These questions will be addressed in models of genetically modified mice and receptor-independent macrophage stimulation. Experimental systems will include in vitro and in vivo investigation of DC and T-cell function.