Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.

Abstract

The ingestion of foreign material-phagocytosis-is a fundamental feature shared across phyla, from single-celled ameba to more complex mammalian cells. Phagocytosis is a crucial process for maintaining homeostasis in body systems, including in the central nervous system (CNS). In this review, we first explore how phagocytic cells maintain CNS homeostasis by removing excess synapses, apoptotic cells, and debris. Next, we discuss the dual role of phagocytosis in CNS pathologies, including multiple sclerosis, aging, Alzheimer's disease, traumatic CNS injury, and ischemic stroke. During CNS pathology, phagocytosis aids debris removal and tissue repair, yet also contributes to damage through the engulfment of viable synapses and cells and via the release of cytotoxic mediators. Finally, we highlight current clinically relevant approaches and consider future directions for leveraging phagocytosis to enhance CNS repair and improve neurologic outcomes.