Abstract
Fungal diseases of the central nervous system (CNS) are associated with severe neurological damage and death in immunocompromised hosts, yet they remain neglected in research and policy. Neuroinflammation, a common clinical feature of fungal infection, has been implicated as a key driver of brain injury, but the mechanisms underlying its contribution to pathology are not well understood. The aim of this Review is to discuss the double-edged role of neuroinflammation in the pathogenesis of fungal infections. We provide an overview of the immune barriers that protect the CNS from fungal infection, the fungal strategies that enable immune evasion and neuroinvasion, and the complex mechanisms underlying the development of neuroinflammation during fungal infection. Finally, we explore how both insufficient and excessive neuroinflammatory responses drive neuropathology, and we conclude by outlining current challenges as well as potential directions for advancing future research in this overlooked field.