The innate immune system and the clearance of apoptotic cells

Removal of unwanted, effete, or damaged cells through apoptosis, an active cell death culminating in phagocytic removal of cell corpses, is an important process throughout the immune system in development, control, and homeostasis. For example, neutrophil apoptosis is central to the resolution of acute inflammation, whereas autoreactive and virus-infected cells are similarly deleted. The AC removal process functions not only to remove cell corpses but further, to control inappropriate immune responses so that ACs are removed in an anti-inflammatory manner. Such ″silent″ clearance is mediated by the innate immune system via polarized monocyte/macrophage populations that use a range of PRRs and soluble molecules to promote binding and phagocytosis of ACs. Additionally, attractive signals are released from dying cells to recruit phagocytes to sites of death. Here, we review the molecular mechanisms associated with innate immune removal of and responses to ACs and outline how these may impact on tissue homeostasis and age-associated pathology (e.g., cardiovascular disease). Furthermore, we discuss how an aging innate immune system may contribute to the inflammatory consequences of aging and why the study of an aging immune system may be a useful path to advance characterization of mechanisms mediating effective AC clearance.