Fetal brain response to maternal inflammation requires microglia

In uteroinfection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal central nervous system infection, is associated with an increased risk of autism and schizophrenia in affected offspring. The cell types mediating the response of the fetal brain to maternal inflammation are largely unknown, hindering the development of therapies to prevent and treat adverse neuropsychiatric outcomes. Here, we show that microglia, the resident phagocytes of the brain, are enriched for expression of receptors for relevant pathogens and cytokines, throughout embryonic development. Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant dams, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life. We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA. These findings demonstrate that microglia play a critical, durable role in fetal response to maternal inflammation, pointing at microglia as a potential therapeutic cell target.