Fig. 1

Multiple biological functions of microglia. A Microglia in brain development and neurogenesis. CD11c⁺ microglia are critical for neurodevelopment by providing pro-survival IGF-1 signaling for newborn neurons and oligodendrocytes. They also phagocytose apoptotic neurons, excessive myelin sheath and oligodendrocyte precursor cells to accomplish a structure–function equilibrium within neural circuits. B Immune surveillance and homeostasis. Microglia perform a dual-scale surveillance of CNS homeostasis by their processes sensitive to environmental perturbations. They are pivotal immune components in CNS infection and autoimmune diseases. C Microglia regulate angiogenesis and cerebral blood flow. Tissue stiffness and O₂ concentration are two important cues for microglia to modulate angiogenesis throughout development. Capillary-associated microglia interact with brain vessels via purinergic signaling to maintain appropriate cerebral blood flow. D Dual-role of microglial in BBB integrity. Microglia can rescue BBB damage by secreting claudin 5 and phagocytosing infiltrated neutrophils to ameliorate further brain injury. On the other hand, they also secrete TNF-α to induce degradation of endothelial junctions, which aggravates BBB disruption. E Bi-directional role of microglia as sculptors of synaptic plasticity. Except for synaptic elimination via “eat me” signaling, microglia are also guardians of synaptic structures through “don’t eat me” signaling CD47–SIRPα. They engulf extracellular matrix deposition to support the formation and maturation of dendrite spines. F Microglial phagocytosis and efferocytosis. Microglia detect and phagocytose apoptotic neurons, myelin sheath and Aβ plaque by different receptors. Inside microglia, the phagosomes undergo hybrid phagolysosomes formation, gastrosomes fusion, and gastrosomes contraction to facilitate the scavenging of debris. G Interactions between microglia and other cells. Shared signaling pathways in microglia–other-cells crosstalk include purines, norepinephrine, serotonin, organelle component, complements and cytokines, which exerts profound effect on cellular survival, proliferation, metabolism, and functions. H Microglia durotaxis. Microglia react with the mechanical cues from neural tissue, Aβ plaque and foreign implants via mechanosensors, such as Piezos and integrins. The mechanism and significance of microglial durotaxis remain largely unknown