Microglia in systemic neuroimmune communication: functions beyond phagocytosis

Bidirectional crosstalk between the immune and nervous systems, via 'neuroimmune circuits', regulates homeostatic and inflammatory responses essential for health. Microglia, long-lived brain macrophages, act as key hubs integrating immune signals into coordinated brain responses by shifting into distinct functional states in response to local and systemic cues. In this review, we focus on how environmental signals shape these microglial states, how microglia influence other brain cells through both direct and indirect mechanisms, and emerging evidence of how microglia are impacted by, and respond to, peripheral changes. We highlight microglia as central players in systemic neuroimmune communication, influencing both brain and peripheral health, while outlining recent tools and key knowledge gaps to guide future research into mechanisms of neuroimmune circuit communication.