Principles of neuroanatomical architecture supporting brain–immune cell–cell interactions

Abstract

AbstractThe brain interacts with the immune system under inflammatory and non‐inflammatory conditions. Brain cells have the capacity to produce a variety of cytokines in response to systemic immune activation. Therefore, we hypothesized that brain cells and immune cells move close to each other, so that they can carry out intercellular interactions. In the present article, I review our studies to determine the site for the brain–immune cell–cell interactions. The leptomeninges, choroid plexus stroma and epithelium, attachments of the choroid plexuses, vascular endothelial cells, cells of the perivascular space, and astrocytic end‐feet compose the histological architecture that supports interactions between bone marrow‐derived myeloid cells and brain parenchymal cells under non‐inflammatory conditions. This architecture also functions as the interface at which systemic inflammation‐induced responses can be conveyed to the brain parenchyma under inflammatory conditions. It should be noted that such brain–immune interactions occur in the absence of florid inflammatory cell infiltrates in the brain parenchyma, and with relative preservation of the blood‐brain barrier. Rather, cells comprising the blood‐brain barrier act as the interface linking peripheral immune activation and brain responses. These responses, known as “neuroinflammation”, are unique to the brain. Neuroinflammation differs from the histological inflammation that is accompanied by a florid infiltration of the leptomeninges (meningitis) and/or brain parenchyma (encephalitis) by inflammatory cells. In this review, the relevance of histological studies to unravel the mechanisms linking systemic inflammation, brain–immune interface cells and brain parenchymal cells, with a special emphasis on sepsis‐associated encephalopathy, is discussed.