Microglial tissue surveillance: The never-resting gardener in the developing and adult CNS

Immunosurveillance by microglia is a dynamic process in the central nervous system (CNS) with versatile functions to maintain tissue homeostasis and provide immune defense. A tightly controlled microglia network throughout the CNS parenchyma facilitates efficient immunosurveillance, where each cell guards a certain tissue territory. Each cell is constantly surveilling its environment and the surrounding cells, screening for pathogens but also removing cell debris and metabolites, grooming neighboring cells and facilitating cellular crosstalk. In the absence of inflammation, this "tissue surveillance" by microglia presents an essential process for CNS homeostasis and development. In this review, we provide a summary on different tissue surveillance functions mediated by microglia, the underlying molecular machineries, and how defects, such as genetic mutations, can alter these surveillance mechanisms and cause disease onset.