Regulation of neutrophil migration by tissue macrophages

巨噬细胞和中性粒细胞是先天免疫系统的关键细胞组分。这些免疫细胞迁移的改变与严重的疾病和对感染的高度易感性有关。我们最近发现这些吞噬细胞之间的细胞通讯对于中性粒细胞迁移和抗感染的防御起着至关重要的作用（Schiwon，M.等人Cell 156，456-468，2014）。初步实验表明，巨噬细胞与浸润性中性粒细胞聚集（未发表的观察结果，本提案中的图2），这一过程可能是管理细胞通讯的基础。这种时空通讯可能对促进中性粒细胞的免疫过程以防止感染传播也至关重要。此外，这种通信也可能调节中性粒细胞的反应，以防止附带损害。在这个建议中，我们将调查的机制和作用，这种时空细胞串扰随后中性粒细胞迁移到感染灶，采用新的转基因小鼠和先进的尖端实时体内技术。我们的研究结果将为巨噬细胞和中性粒细胞之间的细胞通讯概念提供新的见解，以推进目前对细菌感染中中性粒细胞调控的认识。

Macrophages and neutrophils are key cellular components of the innate immune system. An altered migration of these immune cells is associated with severe disorders and high susceptibility to infections. We could show very recently the crucial role of the cellular communication between these phagocytes for neutrophil migration and the defense against infections (Schiwon, M. et al. Cell 156, 456-468, 2014). Preliminary experiments show that macrophages cluster with infiltrating neutrophils (unpublished observations, Figure 2 in this proposal), a process likely to be fundamental in administrating the cellular communication. This spatio-temporal communication might also be crucial to boost immunologic processes in neutrophils to prevent spreading of infection. Moreover, such communication might also regulate neutrophil responses to prevent collateral damage. In this proposal, we will investigate the mechanisms and the role of this spatio-temporal cellular crosstalk for subsequent neutrophil migration towards infected foci by employing novel transgenic mice and sophisticated cutting edge real-time in vivo technologies. Our findings will provide novel insights into the concept of cellular communication between macrophages and neutrophils to advance the current knowledge on the regulation of neutrophils in bacterial infections.