Eaten alive! Cell death by primary phagocytosis: ‘phagoptosis’

Phagoptosis, also called primary phagocytosis, is a recently recognised form of cell death caused by phagocytosis of viable cells, resulting in their destruction. It is provoked by exposure of ‘eat-me’ signals and/or loss of ‘don’t-eat-me’ signals by viable cells, causing their phagocytosis by phagocytes. Phagoptosis mediates turnover of erythrocytes, neutrophils and other cells, and thus is quantitatively one of the main forms of cell death in the body. It defends against pathogens and regulates inflammation and immunity. However, recent results indicate that inflamed microglia eat viable brain neurons in models of neurodegeneration, and cancer cells can evade phagocytosis by expressing a ‘don’t-eat-me’ signal, suggesting that too much or too little phagoptosis can contribute to pathology. This review provides an overview of the molecular signals that regulate phagoptosis and the physiological and pathological circumstances in which it has been observed.