Innate apoptotic immunity: the calming touch of death

Apoptotic cell death is an essential and highly ordered process that contributes to both the development and the homeostasis of multicellular organisms. It is associated with dramatic biochemical and cell biological events within the dying cell, including fragmentation of the nucleus and the redistribution of intracellular proteins and membrane lipids. It has long been apparent that phagocytic clearance of the cell corpse is an integral part of the apoptotic process; apoptotic clearance also may be essential in tissue homeostasis. During the cell death process, apoptotic cells acquire new cell surface determinants for specific recognition by responder phagocytes and suppression of immune responsiveness. Recent studies indicate that these determinants are well conserved throughout metazoan evolution; remarkably, their recognition shows no species-specific restriction. Professional and non-professional phagocytes recognize and respond to apoptotic cells similarly, notably with the immediate-early transcriptional repression of a variety of specific genes including those encoding inflammatory cytokines. Secondary responses following engulfment of the apoptotic corpse, utilizing several distinct mechanisms, enhance and sustain this apoptotic suppression. In this review, we highlight the central role of apoptotic cells in innate homeostatic regulation of immunity.