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Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss

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...

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Autores principales: Xia, Anping, Thai, Anthony, Cao, Zhixin, Chen, Xiaohua, Chen, Jing, Bacacao, Brian, Bekale, Laurent A., Schiel, Viktoria, Bollyky, Paul L., Maria, Peter L. Santa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465898/
https://www.ncbi.nlm.nih.gov/pubmed/36096817
http://dx.doi.org/10.1186/s12974-022-02585-w
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author Xia, Anping
Thai, Anthony
Cao, Zhixin
Chen, Xiaohua
Chen, Jing
Bacacao, Brian
Bekale, Laurent A.
Schiel, Viktoria
Bollyky, Paul L.
Maria, Peter L. Santa
author_facet Xia, Anping
Thai, Anthony
Cao, Zhixin
Chen, Xiaohua
Chen, Jing
Bacacao, Brian
Bekale, Laurent A.
Schiel, Viktoria
Bollyky, Paul L.
Maria, Peter L. Santa
author_sort Xia, Anping
collection PubMed
description 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02585-w.
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spelling pubmed-94658982022-09-13 Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss Xia, Anping Thai, Anthony Cao, Zhixin Chen, Xiaohua Chen, Jing Bacacao, Brian Bekale, Laurent A. Schiel, Viktoria Bollyky, Paul L. Maria, Peter L. Santa J Neuroinflammation Research 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02585-w. BioMed Central 2022-09-12 /pmc/articles/PMC9465898/ /pubmed/36096817 http://dx.doi.org/10.1186/s12974-022-02585-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Xia, Anping
Thai, Anthony
Cao, Zhixin
Chen, Xiaohua
Chen, Jing
Bacacao, Brian
Bekale, Laurent A.
Schiel, Viktoria
Bollyky, Paul L.
Maria, Peter L. Santa
Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
title Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
title_full Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
title_fullStr Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
title_full_unstemmed Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
title_short Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
title_sort chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465898/
https://www.ncbi.nlm.nih.gov/pubmed/36096817
http://dx.doi.org/10.1186/s12974-022-02585-w
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