Division of Otolaryngology, Head and Neck Surgery, School of Medicine 0666, University of California, San Diego, La Jolla, CA 92093.
Hear Res. 2022 Jun;419:108518. doi: 10.1016/j.heares.2022.108518. Epub 2022 May 11.
The inner ear, like all organs, interacts with the systemic immune system via lymphatic drainage and vascular circulation to protect itself from infections and stress such as acoustic trauma. The adult mammalian inner ear including the endolymphatic sac is populated with bone-marrow derived resident macrophages. Circulating macrophages continually renew the resident macrophage population. Cells within the endolymphatic sac participate in and affect inner ear immune responses, but specific mechanisms for the interactions are unknown. Resident macrophages are present within the cochlear modiolus, spiral ligament, stria vascularis, on the scala tympani surface of the basilar membrane and in the vestibular ganglia and connective tissue of the vestibular sensory epithelia. In general, the mammalian organ of Corti, on the other hand, does not contain resident macrophages. Although repair of the epithelium following hair cell death is performed by adjacent supporting cells, macrophages in the osseous spiral lamina have been seen to extend processes into the organ of Corti below the inner hair cells where they may assist in reducing synaptopathy. Systemic and middle ear bacterial infections, experimentally simulated by lipopolysaccharide (LPS) injections, cause circulating inflammatory cells to enter the inner ear from venules in the spiral ligament and modiolus. Presumably, this is a surveillance mechanism, and in the absence of cochlear infection, no action is taken, but if noise trauma or ototoxic drug exposure occurs simultaneously, a more aggressive immune response is mounted. Acoustic trauma alone induces influx of circulating immune cells. Vigorous immune responses to pathogens within the cochlea result in fibrotic tissue and osteoid formation within the fluid-filled inner ear spaces. Many of the signals for recruiting and activating immune cells have been identified, but little is known about exactly what the activated cells do, how they interact with resident macrophages and what signals terminate their activity.
内耳与所有器官一样，通过淋巴引流和血管循环与全身免疫系统相互作用，以保护自身免受感染和压力（如声创伤）的影响。成年哺乳动物的内耳（包括内淋巴囊）中充满了骨髓衍生的常驻巨噬细胞。循环巨噬细胞不断更新常驻巨噬细胞群体。内淋巴囊中存在的细胞参与并影响内耳免疫反应，但相互作用的具体机制尚不清楚。常驻巨噬细胞存在于耳蜗轴索、螺旋韧带、血管纹、基底膜的鼓阶表面以及前庭神经节和前庭感觉上皮的结缔组织中。一般来说，另一方面，哺乳动物的柯蒂氏器不含常驻巨噬细胞。虽然毛细胞死亡后的上皮修复是由相邻的支持细胞完成的，但已经观察到骨螺旋板中的巨噬细胞伸出突起进入内毛细胞下方的柯蒂氏器，它们可能有助于减少突触病。系统性和中耳细菌感染，通过脂多糖 (LPS) 注射实验模拟，导致循环炎症细胞从螺旋韧带和轴索中的小静脉进入内耳。推测这是一种监视机制，在没有耳蜗感染的情况下，不会采取任何行动，但如果同时发生噪声创伤或耳毒性药物暴露，就会引发更具攻击性的免疫反应。单纯的声创伤会诱导循环免疫细胞的流入。内耳中病原体的强烈免疫反应会导致纤维组织和骨样物质在内耳充满液体的空间中形成。已经确定了许多招募和激活免疫细胞的信号，但对于激活的细胞具体做什么、它们如何与常驻巨噬细胞相互作用以及什么信号终止它们的活动，知之甚少。
