Nuclear adaptation to intracellular mechanical forces regulates the phagocytic capacity of Drosophila macrophages in vivo

How macrophages fine-tune their appetite to fulfil their clearance role is incompletely understood. Phagocytosis exacerbates cytoplasmic crowding, but whether macrophages can sense this increase and use it to regulate their phagocytic capacity has never been investigated. Here, we test the hypothesis that phagosomes exert a strain on the nucleus, which in turn responds to the intracellular mechanical inputs influencing macrophage appetite. Combining genetic manipulation and live in vivo imaging, we show that engulfed apoptotic bodies indent and deform the nucleus of Drosophila embryonic macrophages, and that phagocytosis increases Lamin B levels. Importantly, we show that silencing Lamin B or components of the LINC complex negatively regulates apoptotic body engulfment in vivo. Thus, we demonstrate that phagosome-induced nuclear molecular and mechanical adaptations are critical for Drosophila embryonic macrophages to sustain apoptotic corpse uptake, thereby unveiling a role for nuclear plasticity in the regulation of macrophage phagocytic capacity in vivo.