Macrophages form integrin-mediated adhesion rings to pinch off surface-bound objects for phagocytosis

Abstract

AbstractMacrophages engulf micron-sized objects including pathogens and cell debris by phagocytosis, serving a fundamental role in immune defense and homeostasis1, 2. Although the internalization process of suspended particles has been thoroughly investigated3, 4, it is incompletely understood how macrophages internalize surface-bound objects by overcoming the surface binding. Here, we prepared a force-sensing platform which visualizes cell-substrate adhesive force by fluorescence. Macrophages are tested on this platform with micron-sized objects (E. coli, microbeads and silver nanorods) immobilized. By co-imaging integrin-transmitted forces and corresponding structural proteins, we discovered that macrophages consistently form integrin-mediated adhesion structures on the surface to encircle and pinch off surface-bound objects. We termed these structures phagocytic adhesion rings (PAR) and showed that integrin tensions in PARs are resulted from local actin polymerization, but not from myosin II. We further demonstrated that the intensity of integrin tensions in PARs is correlated with the object surface-bound strength, and the integrin ligand strength (dictating the upper limit of integrin tensions) determines the phagocytosis efficiency. Collectively, this study revealed a new phagocytosis mechanism that macrophages form PARs to provide physical anchorage for local F-actin polymerization that pushes and lifts off surface-bound objects during phagocytosis.