Phagocytic clearance of apoptotic, necrotic, necroptotic and pyroptotic cells

Although millions of cells in the human body will undergo programmed cell death each day, dying cells are rarely detected under homeostatic settings in vivo. The swift removal of dying cells is due to the rapid recruitment of phagocytes to the site of cell death which then recognise and engulf the dying cell. Apoptotic cell clearance — the engulfment of apoptotic cells by phagocytes — is a well-defined process governed by a series of molecular factors including ‘find-me’, ‘eat-me’, ‘don't eat-me’ and ‘good-bye’ signals. However, in recent years with the rapid expansion of the cell death field, the removal of other necrotic-like cell types has drawn much attention. Depending on the type of death, dying cells employ different mechanisms to facilitate engulfment and elicit varying functional impacts on the phagocyte, from wound healing responses to inflammatory cytokine secretion. Nevertheless, despite the mechanism of death, the clearance of dying cells is a fundamental process required to prevent the uncontrolled release of pro-inflammatory mediators and inflammatory disease. This mini-review summarises the current understandings of: (i) apoptotic, necrotic, necroptotic and pyroptotic cell clearance; (ii) the functional consequences of dying cell engulfment and; (iii) the outstanding questions in the field.