Pattern recognition in phagocytic clearance of altered self

Cells that are unnecessary or harmful to our body emerge in substantial numbers throughout our life. Such "unwanted" cells need to be promptly and selectively removed for tissue homeostasis to be maintained. Most of those cells are induced to undergo physiologic cell death, i.e., apoptosis, and subsequently eliminated by phagocytosis. Target selectivity in this phagocytosis reaction comes from the specific cell-cell interaction between phagocytes and dying cells. The surface structure of apoptotic cells is altered during the death pathway so that they become pattern recognizable as "altered self" by phagocytes, and such surface structures are sometimes called ACAMPs for apoptotic cell-associated molecular patterns. ACAMPs arise either from the exofacial exposure of endogenous molecules or the modification of preexisting surface molecules. Pattern-recognizing phagocytosis receptors present at the surface of phagocytes specifically bind, either directly or indirectly with an aid of bridge molecules, to ACAMPs and transmit signals to induce phagocytosis of bound apoptotic cells. Phagocytes often evoke subsequent actions, rather than simply digesting engulfed apoptotic cells, for a finer tuning of tissue homeostasis. In contrast, precise mechanisms and consequences of cells undergoing nonapoptotic death, i.e., necrosis or autophagy-related death, are less well understood.