ABSTRACT

Cells undergo apoptosis during development, tissue homeostasis and disease, and are subsequently cleared by professional and non-professional phagocytes in a multi-step process, termed eff erocytosis. Recognition involves an ever increasing plethora of apoptotic cell ligands, bridge molecules and phagocyte receptors. Th eir individual contribution to apoptotic cell uptake and ensuing immunological consequences is an important area for future research. Comparatively little is known about the engulfment and digestion of apoptotic cells within phagocytes. Th is is an important evolving area of research which off ers enormous potential for a better understanding of macrophage function in general, and scope to manipulate the clearance process for therapeutic gain. Effi cient clearance of apoptotic cells is critical for tissue homeostasis and controlling the immune response to infl ammatory and infective stimuli. Th is is most poignantly illustrated by pathogens and tumours that are able to exploit the immune-inhibitory signals

of apoptotic cell phagocytosis to aid their survival. In this chapter, we will provide a brief overview of the individual stages of the clearance process, with particular emphasis on, until recently, the largely ignored areas of phagosome maturation and digestion. Th is will be followed by a brief description of the immunological consequences of appropriate versus failed apoptotic cell clearance. Overall, we believe this will illustrate that a better understanding of eff erocytosis may enable the development of novel therapies to treat infl ammatory and autoimmune disease, and prevent inappropriate immune inhibition by pathogens and tumours.