From sensing to shaping: microglial responses in the pathogenesis of viral encephalitis

Viral encephalitis (VE) is a universal menace accounting for severe morbidity and mortality among the affected individuals. VE is the cerebral inflammation triggered by viral infections. In the central nervous system, microglia are the frontline responders that provide defense against invading pathogens, such as neurotropic viruses. Upon viral recognition, microglia become activated and mount antiviral immune responses by producing type I interferons, presenting viral antigens to T cells, and phagocytosing viral components and virus-infected cells during the acute phase of infection. However, if this activation remains exaggerated and chronic, it can lead to severe neuroinflammation, resulting in neuronal cell damage and breach of the blood-brain barrier integrity, allowing invasion of the immune cells further into the brain. So, the purpose of this review is to integrate the existing findings on these bifunctional activation states of microglia and how they determine the pathological consequences of VE, microglial interconnections with other residing cells of the brain, molecular and metabolic regulators of the microglial function, and the therapeutic approaches directed towards restraining microglia-mediated grievous neuroinflammation, enabling host-protection during VE.