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

点击翻译按钮获取中文摘要

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.