Cochlear supporting cells function as macrophage-like cells and protect audiosensory receptor hair cells from pathogens
Cochlear supporting cells function as macrophage-like cells and protect audiosensory receptor hair cells from pathogens
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DOI：
10.1038/s41598-020-63654-9
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发表时间：
2020-04-21
影响因子：
4.6
通讯作者：
Tanaka, Nobuyuki
中科院分区：
文献类型：
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作者：
Hayashi, Yushi;Suzuki, Hidenori;Tanaka, Nobuyuki
为了保护听觉器官免受免疫系统的组织损伤，内耳通过血迷路屏障与循环免疫系统分开，该屏障以前被认为是免疫特权部位。近年来研究表明，巨噬细胞分布于耳蜗，尤其是螺旋韧带、螺旋神经节、血管纹；然而，听觉受体毛细胞（HC）使用的直接病原体防御机制仍然不清楚。在这里，我们发现 HC 受到周围辅助支持细胞 (SC) 和大上皮嵴（GER 或科利克氏器）细胞 (GERC) 的保护，免受病原体侵害。在分离的小鼠耳蜗感觉上皮中，我们建立了泰勒氏小鼠脑脊髓炎病毒，该病毒感染 SC 和 GERC，但很少感染 HC。病毒感染的 SC 产生干扰素 (IFN)-α/β，并且病毒有效地感染 IFN-α/β 受体无效的感觉上皮中的 HC。有趣的是，病毒感染的 SC 和 GERC 表达巨噬细胞标记蛋白，并通过细胞脱离从细胞层中消除。此外，脂多糖诱导SCs的吞噬作用而没有细胞脱离，并且SCs吞噬细菌。这些结果表明，SCs 具有类似巨噬细胞的功能，可以保护邻近的 HC 免受病原体侵害，并提供一种新型的抗感染内耳免疫系统。
To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site. Recent studies have shown that macrophages are distributed in the cochlea, especially in the spiral ligament, spiral ganglion, and stria vascularis; however, the direct pathogen defence mechanism used by audiosensory receptor hair cells (HCs) has remained obscure. Here, we show that HCs are protected from pathogens by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kolliker's organ) cells (GERCs). In isolated murine cochlear sensory epithelium, we established Theiler's murine encephalomyelitis virus, which infected the SCs and GERCs, but very few HCs. The virus-infected SCs produced interferon (IFN)-alpha/beta, and the viruses efficiently infected the HCs in the IFN-alpha/beta receptor-null sensory epithelium. Interestingly, the virus-infected SCs and GERCs expressed macrophage marker proteins and were eliminated from the cell layer by cell detachment. Moreover, lipopolysaccharide induced phagocytosis of the SCs without cell detachment, and the SCs phagocytosed the bacteria. These results reveal that SCs function as macrophage-like cells, protect adjacent HCs from pathogens, and provide a novel anti-infection inner ear immune system.