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

TL;DR

Mast cells in the meninges help fight viral infections by working with stromal cells and boosting immune responses.

Contribution

This study identifies mast cells' role in antiviral immunity in the meninges through IL-33 signaling and stromal cell communication.

Findings

Mast cells in the meninges mature post-weaning and are distributed along meningeal vasculature.

Mast cells enhance antiviral immunity by promoting CD8+ T cell infiltration and viral clearance via IL-33 signaling.

Stromal cell-derived IL-33 and ATP synergistically activate mast cells to upregulate cytokines and chemokines.

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.

This study delineates the spatial distribution and postnatal maturation of meningeal mast cells and uncovers their essential role in antiviral immunity. Using genetic models, mast cells are shown to promote CD8⁺ T cell infiltration and viral clearance via IL‐33 receptor signaling and synergistic activation by IL‐33 and ATP from infected stromal cells.

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