VE refers to acute intracranial inflammatory lesions and involves the meninges and brain parenchyma. Various viruses invade the CNS through blood/lymphoid circulation and peripheral nerve migration. Damaged neurons release signals (such as ATP and cytokines) to recruit microglia, which initiate innate immunity ①. Cytokines and chemokines are released from activated microglia (Act-Mig) and astrocytes (see text for details). Thereafter, peripheral neutrophils (Neu), monocytes (Mo), and APCs (including DCs) infiltrate the brain parenchyma via increased BBB permeability. IFN is produced to enlarge the antiviral effects and APCs present antigens to T cells and later to B cells, constituting adaptive immunity ②. CD8^{+} T cells produce granzyme and perforin to clear infected cells, including neurons, vascular endothelial cells, and pericytes. Plasmacytes differentiated from mature B cells secrete specific IgM and IgG antibodies to neutralize viral particles and restrict their spread. Meningeal immunity ③ has also recently been reported to play an important role in VE. Both myeloid and B cells differentiate from HSCs, which originate from skull bone marrow (BM) or meninges, and meningeal macrophages (MMs) extravasate from the pia mater or cross the arachnoid mater into the brain parenchyma. Additionally, viruses can infect and transmit from MLVs into CLNs to enhance peripheral immunity. Red arrow: Viral invasion/transmission; Blue arrow: Immune cell infiltration.
【저자키워드】 experimental animal models, viral encephalitis, neurotropic viruses, Meningeal immunity,