Perineural immune environment of olfactory nerves is reshaped by neuroinflammatory drainage and connects to ethmoid bone marrow

Cerebrospinal fluid (CSF) contains inflammatory cues that enable peripheral immune surveillance of the central nervous system (CNS). While some cranial nerves allow for CSF efflux, the immune environment around CSF-interfacing cranial nerves during neuroinflammation is still poorly understood. Using a mouse model of multiple sclerosis [experimental autoimmune encephalomyelitis (EAE)] and CNS Mycobacterium tuberculosis infection (CNS-Mtb), we examined immune responses around olfactory nerve bundles near the cribriform plate, a key CSF efflux route. During neuroinflammation, we found increased perineural immune cells that had access to intracranial injected beads, dye, and bacteria. Additionally, we identified osseous channels connecting the environment surrounding olfactory nerves to bone marrow in the cribriform plate (cpBM). Notably, the cpBM undergoes myelopoiesis during EAE, has access to components of intracranial drainage, and is vulnerable to Mtb bacteria invasion during CNS-Mtb infection. Our findings improve the understanding of how the environments of CSF-interfacing cranial nerves and bone marrow are altered within the skull during neuroinflammatory disease.