Meningeal macrophages protect against viral neuroinfection.

The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II- MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.

Meningeal regulation of infections: A double-edged sword.

In the past 10 years, important discoveries have been made in the field of neuroimmunology, especially regarding brain borders. Indeed, meninges are protective envelopes surrounding the CNS and are currently in the spotlight, with multiple studies showing their involvement in brain infection and cognitive disorders. In this review, we describe the meningeal layers and their protective role in the CNS against bacterial, viral, fungal, and parasitic infections, by immune and nonimmune cells. Moreover, we discuss the neurological and cognitive consequences resulting from meningeal infections in neonates (e.g. infection with group B Streptococcus, cytomegalovirus, …) or adults (e.g. infection with Trypanosoma brucei, Streptococcus pneumoniae, …). We hope that this review will bring to light an integrated view of meningeal immune regulations during CNS infections and their neurological consequences.