Nuclear plasticity regulates macrophage phagocytic capacity in vivo

Abstract

Macrophages fine-tune their appetite to fulfil their clearance role, but how they achieve this is incompletely understood. The nucleus can sense and respond to extracellular physical challenges, but whether it can also detect and react to intracellular mechanical inputs is unclear. Here, we tested the hypothesis that phagosomes exert a strain on the nucleus, and that the consequent nuclear mechanoresponse influences macrophage appetite. Combining genetic manipulation and live in vivo imaging, we show that engulfed apoptotic bodies indent the nucleus of Drosophila embryonic macrophages, leading to nuclear deformation and causing an increase in Lamin B levels. We demonstrate that these phagosome-induced nuclear molecular and mechanical adaptations are critical for macrophages to sustain uptake - unveiling a role for nuclear plasticity in the regulation of macrophage phagocytic capacity in vivo.