Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders

The immune and nervous systems have unique developmental trajectories that individually build intricate networks of cells with highly specialized functions. These two systems have extensive mechanistic overlap and frequently coordinate to accomplish the proper growth and maturation of an organism. Brain resident innate immune cells - microglia - have the capacity to sculpt neural circuitry and coordinate copious and diverse neurodevelopmental processes. Moreover, many immune cells and immune-related signalling molecules are found in the developing nervous system and contribute to healthy neurodevelopment. In particular, many components of the innate immune system, including Toll-like receptors, cytokines, inflammasomes and phagocytic signals, are critical contributors to healthy brain development. Accordingly, dysfunction in innate immune signalling pathways has been functionally linked to many neurodevelopmental disorders, including autism and schizophrenia. This review discusses the essential roles of microglia and innate immune signalling in the assembly and maintenance of a properly functioning nervous system.