Activated tissue-resident macrophages contribute to hair cell insults in noise-induced hearing loss

Abstract

Abstract Background Macrophages serve as the primary immune cell population and assume a pivotal role in the immune response within the damaged cochleae, yet the origin and role of macrophages in response to noise exposure remains controversial. Methods We generated Ccr2RFP/+ Cx3cr1GFP/+ dual-reporter mice to identify the infiltrated and tissue-resident macrophages in the noise-exposed cochlea. Results Under steady-state, tissue-resident macrophages present in the Rosenthal's canal (SGNs), spiral ligament, and basilar membrane of the adult cochlea. After noise exposure, activated resident macrophages change in morphology, increase in abundance, and migrate to the region of hair cells, leading to the loss of outer hair cells and the damage of ribbon synapses. Meanwhile, peripheral monocytes are not implicated in the noise-induced hair cell insults. Furthermore, the noise-induced activity and redistribution of macrophages were abolished by the inhibition of TLR4 signaling, resulting in alleviated insults of hair cells and partial recovery of hearing function. Conclusions Our findings point to cochlea resident macrophages as pro-inflammatory and detrimental players in acoustic trauma and introduce a potential therapeutic target in noise-induced hearing loss.