A crosstalk between adhesion and phagocytosis integrates macrophage functions into their microenvironment

Phagocytosis is the process of actin-dependent internalization and degradation of large particles. Macrophages, which are professional phagocytes, are present in all tissues and are, thus, exposed to environments with different mechanical properties. How mechanical cues from macrophages’ environment affect their ability to phagocytose and, in turn, how phagocytosis influences how phagocytic cells interact with their environment remain poorly understood. We found that the ability of macrophages to perform phagocytosis varied with the substrate stiffness. Using live traction force microscopy, we showed that phagocytosing macrophages applied more dynamic traction forces to their substrate. In addition, integrin-mediated phagocytosis triggered a transient loss of podosomes that was associated with decreased degradation of the extracellular matrix, concomitantly with RhoA activation and F-actin recruitment at phagocytic cups. Overall, these results highlight a crosstalk between macrophage phagocytosis and cell adhesion. Mechanical properties of the microenvironment influence phagocytosis, which, in turn, impacts how macrophages interact with their surroundings.