Why do central nervous system barriers host a diverse immune landscape?

The meninges in vertebrates comprise three layers (dura, arachnoid, pia mater), representing an important barrier surrounding and protecting the central nervous system (CNS). The most exterior CNS barrier, the dura mater, is unique because it resembles a peripheral tissue. It hosts a rich immune landscape, lymphatic vessels, and fenestrated vasculature, allowing microbes and other threats from the blood to extravasate into the meninges, potentially reaching the underlying CNS. The highly specialized large venous drainage system in the dura is especially susceptible to infection. Here, we explore specializations in the CNS barrier system from an anatomical and immunological perspective and posit that the dura mater evolved an elaborate innate and adaptive immune system in specific locations within it to protect underlying CNS tissue against invading pathogens.