Phagocytosis in the Brain: Homeostasis and Disease

Abstract

Microglia are resident macrophages of the central nervous system and significantly contribute to overall brain function by participating in phagocytosis during development, homeostasis, and diseased states. Phagocytosis is a highly complex process that is specialized for the uptake and removal of opsonized and non-opsonized targets, such as pathogens, apoptotic cells, and cellular debris. While the role of phagocytosis in mediating classical innate and adaptive immune responses has been known for decades, it is now appreciated that phagocytosis is also critical throughout early neural development, homeostasis, and initiating repair mechanisms. As such, modulating phagocytic processes has provided unexplored avenues with the intent of developing novel therapeutics that promote repair and regeneration in the CNS. Here, we review the functional consequences that phagocytosis plays in both the healthy and diseased CNS, and summarize how phagocytosis contributes to overall pathophysiological mechanisms involved in brain injury and repair.

Keywords: macrophage; microglia; neurodegeneration; neuroinflammation; phagocytosis.

Figure 1

Microglial Phagocytosis in the CNS. During development, microglial phagocytosis is essential for the refinement of excessive synapses, as well as the removal of apoptotic neurons and oligodendrocytes that are overproduced during development. Homeostatic microglia in the adult brain constantly survey the brain's parenchyma, contributing to synaptic plasticity and phagocytosing apoptotic progenitor cells. With advanced age, microglia undergo senescence, display impaired debris clearance, and excessively prune synapses. In diseases, such as Alzheimer's or multiple sclerosis, microglia act as key contributors to pathology, which is partially mediated by phagocytosis of substrates, such as amyloid-β or myelin debris (made in ©BioRender - biorender.com).