Stromal Cell-Mast Cell Communication Orchestrates Anti-Viral Immunity in the Meninges

Mast cells are tissue-resident immune sentinels. However, their spatial localization and potential role in the antiviral response within the meninges-the protective barrier surrounding the central nervous system-remain unclear. Here, the distribution pattern along meningeal vasculature is maped and identified a post-weaning maturation process. Single-cell RNA sequencing reveals that mast cells mount a robust immune response against LCMV infection. Ablation of mast cells results in reduced CD8⁺ T cell infiltration and impairs viral clearance. Mechanistic dissection identifies a critical role for the IL-33 receptor on mast cells, which responds to IL-33 derived from stromal cells, in mediating antiviral immunity. Further analysis shows that mast cells synergistically upregulate cytokines and chemokines in response to IL-33 and ATP released by virus-infected stromal cells. Collectively, these findings reveal a critical role for mast cells in enhancing meningeal antiviral immunity and highlight potential strategies for brain protection during infection.