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

Abstract 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.