Meningeal inflammation and arachnoid barrier breakdown in a mouse model of neonatal bacterial meningitis.

Abstract

Newborns are especially susceptible to bacterial meningitis, primarily caused by group B Streptococcus (GBS), due to incomplete maturation of immune and barrier systems. While meningitis is well known to break down the blood-brain barrier, its effect on the meningeal arachnoid barrier remains poorly understood. Using a neonatal bacterial meningitis model, we demonstrate that GBS infection significantly increases arachnoid barrier permeability, disrupts tight junctions, and elevates meningeal production of proinflammatory cytokines. CD206⁺/LYVE-1⁺ border-associated macrophages undergo morphological and molecular activation post-infection, but their depletion prior to infection does not attenuate arachnoid barrier leakage or cytokine levels. We show that meningeal fibroblasts are a source of proinflammatory cytokines in response to GBS infection and that a systemic exposure of TNF-α alone is sufficient to induce barrier breakdown. These results support that the neonatal arachnoid barrier is vulnerable to cytokine-induced breakdown and highlight the role of non-immune meningeal cells like fibroblasts during bacterial infection.