Multiple Sclerosis (MS) is characterized by immune-mediated damage to the myelin sheath, disrupting neuronal signaling and permanently damaging the central nervous system (CNS). The vagus nerve has emerged as a key regulator of peripheral inflammatory diseases, with activation or elimination of vagal signaling diminishing or enhancing immune cell activity, respectively, but whether it similarly orchestrates CNS immune responses is only beginning to be explored.

To model the immune-driven demyelination present in MS, susceptible female mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus (JHMV), which results in acute encephalomyelitis and subsequent spinal cord demyelination. To explore the role of the vagus nerve in MS, cohorts of female mice were subject to either a SHAM surgery or left cervical vagotomy (VGX) prior to infection with JHMV. VGX significantly impaired immune cell trafficking to the CNS. At day 7 post-infection, VGX mice exhibited fewer recruited myeloid cells and subsequently significantly less CD4+ and CD8+ T-cells in the brain with elevated viral loads. CD8 T-cell effector function was diminished in VGX mice, as evidenced by reduced interferon gamma production upon stimulation with JHMV-derived peptides.

By day 21 post-infection when demyelination peaks, VGX mice experienced a significant increase in spinal cord demyelination despite a decrease in T-cells within the spinal cord. qPCR of brain tissue highlighted that VGX mice had persistently elevated mRNA transcripts encoding for Jhmv and T-cell chemokines (Cxcl9, Cxcl10), indicating impaired viral clearance compared to SHAM controls.

These data demonstrate that intact vagal signaling is required to mount an appropriate immune response to JHMV, facilitating immune cell recruitment and viral clearance. This work highlights a novel role for the vagus nerve in modulating CNS immunity and suggests therapeutic potential in targeting vagal pathways for MS and related neuroinflammatory diseases.