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Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models

The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored...

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Autores principales: Xu, Kai, Chen, Sen, Xie, Le, Qiu, Yue, Bai, Xue, Liu, Xiao-Zhou, Zhang, Hui-Min, Wang, Xiao-Hui, Jin, Yuan, Sun, Yu, Kong, Wei-Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829512/
https://www.ncbi.nlm.nih.gov/pubmed/33505961
http://dx.doi.org/10.3389/fcell.2020.597769
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author Xu, Kai
Chen, Sen
Xie, Le
Qiu, Yue
Bai, Xue
Liu, Xiao-Zhou
Zhang, Hui-Min
Wang, Xiao-Hui
Jin, Yuan
Sun, Yu
Kong, Wei-Jia
author_facet Xu, Kai
Chen, Sen
Xie, Le
Qiu, Yue
Bai, Xue
Liu, Xiao-Zhou
Zhang, Hui-Min
Wang, Xiao-Hui
Jin, Yuan
Sun, Yu
Kong, Wei-Jia
author_sort Xu, Kai
collection PubMed
description The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2, encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice.
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spelling pubmed-78295122021-01-26 Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models Xu, Kai Chen, Sen Xie, Le Qiu, Yue Bai, Xue Liu, Xiao-Zhou Zhang, Hui-Min Wang, Xiao-Hui Jin, Yuan Sun, Yu Kong, Wei-Jia Front Cell Dev Biol Cell and Developmental Biology The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2, encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7829512/ /pubmed/33505961 http://dx.doi.org/10.3389/fcell.2020.597769 Text en Copyright © 2021 Xu, Chen, Xie, Qiu, Bai, Liu, Zhang, Wang, Jin, Sun and Kong. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Xu, Kai
Chen, Sen
Xie, Le
Qiu, Yue
Bai, Xue
Liu, Xiao-Zhou
Zhang, Hui-Min
Wang, Xiao-Hui
Jin, Yuan
Sun, Yu
Kong, Wei-Jia
Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
title Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
title_full Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
title_fullStr Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
title_full_unstemmed Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
title_short Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
title_sort local macrophage-related immune response is involved in cochlear epithelial damage in distinct gjb2-related hereditary deafness models
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829512/
https://www.ncbi.nlm.nih.gov/pubmed/33505961
http://dx.doi.org/10.3389/fcell.2020.597769
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