Abstract Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues, particularly dural lymphatic vessels that allow cerebrospinal fluid outflow, facilitate intersystem communication. Here we observe that cerebrospinal fluid exits into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria usurp this perivascular route to infect the skull’s hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. Because skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in cerebrospinal fluid by regional marrow has broad implications for neurological disorders. One-Sentence Summary Skull channels transport cerebrospinal fluid from the subarachnoid space to the cranial bone marrow via a perivascular route, which bacteria use during meningitis.

Cerebrospinal fluid outflow through skull channels instructs cranial hematopoiesis