Regulation of neutrophil migration by tissue macrophages

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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 Preliminary experiments show that macrophages cluster with infiltrating neutrophils (unpublished observations, Figure 2 in this proposal), a process likely to be fundamental in administrating the cellular communication.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.