Eat-Me: Autophagy, Phagocytosis, and Reactive Oxygen Species Signaling

Significance: Phagocytosis is required for the clearance of dying cells. The subsequent regulation of inflammatory responses by phagocytic cells is mediated by both innate and adaptive immune responses. Autophagy, an evolutionarily ancient process of lysosomal self-digestion of organelles, protein aggregates, apoptotic corpses, and cytosolic pathogens, has only recently become appreciated for its dynamic relationship with phagocytosis, including newly discovered autophagic-phagocytosis hybrid'' processes such as microtubule-associated protein 1 light chain 3-associated phagocytosis (LAP). Recent Advances: Signal transduction by reactive oxygen species (ROS) plays a critical role in the modulation of autophagy, phagocytosis, and LAP, and serves as both a link and an additional layer of regulation between these processes. Furthermore, specific targets for oxidation by ROS molecules have recently begun to become identified in each of these processes, as have shared'' proteins that facilitate the successful completion of both autophagy and phagocytosis. High mobility group box 1 is at the crossroads of autophagy, phagocytosis, and oxidative stress. Critical Issues: In this review, we discuss the most recent findings that link elements of autophagy and phagocytosis, specifically through redox-dependent signal transduction. These interconnected cellular processes are placed in the context of cell death and immunity in both health and disease. Future Directions: Given the broad roles that autophagy, phagocytosis, and ROS signaling play in human health, disease, and the maintenance of cellular and organismal homeostatic balance, it is important to delineate intersections between these pathways and uncover targets for potential therapeutic intervention in the setting of autoimmune and inflammatory diseases. Antioxid. Redox Signal. 18, 677-691.