Zhang Celia, Frye Mitchell D, Riordan Juliana, Sharma Ashu, Manohar Senthilvelan, Salvi Richard, Sun Wei, Hu Bo Hua
Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA.
Department of Audiology, School of Health Sciences, University of the Pacific, San Francisco, CA, USA.
J Neurosci Res. 2021 Nov;99(11):2999-3020. doi: 10.1002/jnr.24925. Epub 2021 Sep 14.
The cochlea, the sensory organ for hearing, has a protected immune environment, segregated from the systemic immune system by the blood-labyrinth barrier. Previous studies have revealed that acute acoustic injury causes the infiltration of circulating leukocytes into the cochlea. However, the molecular mechanisms controlling immune cell trafficking are poorly understood. Here, we report the role of CX3CR1 in regulating the entry of neutrophils into the cochlea after acoustic trauma. We employed B6.129P-Cx3cr1 /J mice, a transgenic strain that lacks the gene, Cx3cr1, for coding the fractalkine receptor. Our results demonstrate that lack of Cx3cr1 results in the augmentation of neutrophil infiltration into cochlear tissues after exposure to an intense noise of 120 dB SPL for 1 hr. Neutrophil distribution in the cochlea is site specific, and the infiltration level is positively associated with noise intensity. Moreover, neutrophils are short lived and macrophage phagocytosis plays a role in neutrophil clearance, consistent with typical neutrophil dynamics in inflamed non-cochlear tissues. Importantly, our study reveals the potentiation of noise-induced hearing loss and sensory cell loss in Cx3cr1 mice. In wild-type control mice (Cx3cr1 ) exposed to the same noise, we also found neutrophils. However, neutrophils were present primarily inside the microvessels of the cochlea, with only a few in the cochlear tissues. Collectively, our data implicate CX3CR1-mediated signaling in controlling neutrophil migration from the circulation into cochlear tissues and provide a better understanding of the impacts of neutrophils on cochlear responses to acoustic injury.
耳蜗作为听觉的感觉器官，拥有一个受保护的免疫环境，通过血迷路屏障与全身免疫系统隔离开来。先前的研究表明，急性声学损伤会导致循环白细胞浸润到耳蜗中。然而，控制免疫细胞运输的分子机制却知之甚少。在此，我们报告了CX3CR1在调节声学创伤后中性粒细胞进入耳蜗中的作用。我们使用了B6.129P-Cx3cr1/J小鼠，这是一种缺乏编码趋化因子受体的基因Cx3cr1的转基因品系。我们的结果表明，缺乏Cx3cr1会导致在暴露于120 dB SPL的强噪声1小时后，中性粒细胞向耳蜗组织的浸润增加。中性粒细胞在耳蜗中的分布具有部位特异性，并且浸润水平与噪声强度呈正相关。此外，中性粒细胞寿命较短，巨噬细胞吞噬作用在中性粒细胞清除中发挥作用，这与非耳蜗炎症组织中典型的中性粒细胞动态一致。重要的是，我们的研究揭示了Cx3cr1小鼠中噪声诱导的听力损失和感觉细胞损失的增强。在暴露于相同噪声的野生型对照小鼠（Cx3cr1+）中，我们也发现了中性粒细胞。然而，中性粒细胞主要存在于耳蜗的微血管内，耳蜗组织中只有少数。总的来说，我们的数据表明CX3CR1介导的信号传导在控制中性粒细胞从循环进入耳蜗组织中起作用，并为更好地理解中性粒细胞对耳蜗声学损伤反应的影响提供了依据。
