Abstract
The human inner ear, which is segregated by a blood/labyrinth barrier, contains resident macrophages [CD163, ionized calcium-binding adaptor molecule 1 (IBA1)-, and CD68-positive cells] within the connective tissue, neurons, and supporting cells. In the lateral wall of the cochlea, these cells frequently lie close to blood vessels as perivascular macrophages. Macrophages are also shown to be recruited from blood-borne monocytes to damaged and dying hair cells induced by noise, ototoxic drugs, aging, and diphtheria toxin-induced hair cell degeneration. Precise monitoring may be crucial to avoid self-targeting. Macrophage biology has recently shown that populations of resident tissue macrophages may be fundamentally different from circulating macrophages. We removed uniquely preserved human cochleae during surgery for treating petroclival meningioma compressing the brain stem, after ethical consent. Molecular and cellular characterization using immunofluorescence with antibodies against IBA1, TUJ1, CX3CL1, and type IV collagen, and super-resolution structured illumination microscopy (SR-SIM) were made together with transmission electron microscopy. The super-resolution microscopy disclosed remarkable phenotypic variants of IBA1 cells closely associated with the spiral ganglion cells. Monitoring cells adhered to neurons with “synapse-like” specializations and protrusions. Active macrophages migrated occasionally nearby damaged hair cells. Results suggest that the human auditory nerve is under the surveillance and possible neurotrophic stimulation of a well-developed resident macrophage system. It may be alleviated by the non-myelinated nerve soma partly explaining why, in contrary to most mammals, the human’s auditory nerve is conserved following deafferentiation. It makes cochlear implantation possible, for the advantage of the profoundly deaf. The IBA1 cells may serve additional purposes such as immune modulation, waste disposal, and nerve regeneration. Their role in future stem cell-based therapy needs further exploration.
Highlights
The inner ear is an enclave protected by solid bone
The macrophages found resided in the corti tunnel, adhering to the lateral cell surface of the inner pillars near a few dying inner hair cells (IHCs) (Figure 1)
Super-resolution structured illumination microscopy (SR-SIM), using macrophage immunostaining for marker ionized calcium-binding adaptor molecule 1 (IBA1), exposed more clearly their interface with neighboring cells
Summary
The inner ear is an enclave protected by solid bone. Despite its proximity to infection-prone areas, it was long thought to lack active immune responses. Immune-reactive cells or tissue macrophages were found in other areas of the inner ear under steady-state conditions [5,6,7,8]. It is ostensible that the human inner ear possesses resid ent and migratory macrophages [positive for markers CD163, ionized calcium-binding adaptor molecule 1 (IBA1), and CD68] within the connective tissues, neurons, and supporting cells [9]. These cells were characterized as macrophage/microglial cells and were assumed to belong to the innate and adaptive immune system [10]. Tissue macrophages seem to be replaced from bone marrow myeloid precursors [6, 7], whereas brain microglia undergo self-renewal during life [12]
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