Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss

被引:26
作者
Xia, Anping [1 ]
Thai, Anthony [1 ]
Cao, Zhixin [2 ]
Chen, Xiaohua [3 ]
Chen, Jing [1 ]
Bacacao, Brian [1 ]
Bekale, Laurent A. [1 ]
Schiel, Viktoria [1 ]
Bollyky, Paul L. [4 ]
Santa Maria, Peter L. [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Palo Alto, CA 94305 USA
[2] Shandong First Med Univ, Shandong Prov Hosp, Dept Pathol, Jinan, Shandong, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Otolaryngol Head & Neck Surg, Zhengzhou, Henan, Peoples R China
[4] Stanford Univ, Dept Med, Infect Dis, Palo Alto, CA 94305 USA
关键词
CSOM; PA; SNHL; Macrophages; HC loss; Cytokines; ROUND WINDOW MEMBRANE; INNER-EAR; BASILAR-MEMBRANE; RAT ORGAN; COCHLEAR; CELLS; ACTIVATION; CISPLATIN; PERMEABILITY; PATHOGENESIS;
D O I
10.1186/s12974-022-02585-w
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model. Methods We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR. Results We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea. Conclusions Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).
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页数:15
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