Microglia: Immune and non-immune functions.

As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided in their tasks by intricate bidirectional communication with other brain cells under steady-state conditions as well as with infiltrating peripheral immune cells during perturbations. Harmonious cell-cell communication involving microglia are considered crucial to maintain the healthy state of the tissue environment and to overcome pathology such as neuroinflammation. Analyses of such intercellular pathways have contributed to our understanding of the heterogeneous but context-associated microglial responses to environmental cues across neuropathology, including inflammatory conditions such as infections and autoimmunity, as well as immunosuppressive states as seen in brain tumors. Here, we summarize the latest evidence demonstrating how these interactions drive microglia immune and non-immune functions, which coordinate the transition from homeostatic to disease-related cellular states.

Current tools to interrogate microglial biology.

Microglial cells perform a plethora of functions in the central nervous system (CNS), involving them in brain development, maintenance of homeostasis in adulthood, and CNS diseases. Significant technical advancements have prompted the development of novel systems adapted to analyze microglia with increasing specificity and intricacy. The advent of single-cell technologies combined with targeted mouse models has been decisive in deciphering microglia heterogeneity and dissecting microglial functions. However sophisticated these tools have become, clear limitations remain. Understanding their pitfalls and advantages ensures their correct application. Therefore, we provide a guide to the cutting-edge methods currently available to dissect microglial biology.