Putting the brakes on phagocytosis: “don't-eat-me” signaling in physiology and disease

Timely removal of dying or pathogenic cells by phagocytes is essential to maintaining host homeostasis. Phagocytes execute the clearance process with high fidelity while sparing healthy neighboring cells, and this process is at least partially regulated by the balance of “eat-me” and “don't-eat-me” signals expressed on the surface of host cells. Upon contact, eat-me signals activate “pro-phagocytic” receptors expressed on the phagocyte membrane and signal to promote phagocytosis. Conversely, don't-eat-me signals engage “anti-phagocytic” receptors to suppress phagocytosis. We review the current knowledge of don't-eat-me signaling in normal physiology and disease contexts where aberrant don't-eat-me signaling contributes to pathology.