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Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis
Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629241/ https://www.ncbi.nlm.nih.gov/pubmed/34843580 http://dx.doi.org/10.1371/journal.pone.0260443 |
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author | Hayashi, Yushi Suzuki, Hidenori Nakajima, Wataru Uehara, Ikuno Tanimura, Atsuko Himeda, Toshiki Koike, Satoshi Katsuno, Tatsuya Kitajiri, Shin-ichiro Koyanagi, Naoto Kawaguchi, Yasushi Onomoto, Koji Kato, Hiroki Yoneyama, Mitsutoshi Fujita, Takashi Tanaka, Nobuyuki |
author_facet | Hayashi, Yushi Suzuki, Hidenori Nakajima, Wataru Uehara, Ikuno Tanimura, Atsuko Himeda, Toshiki Koike, Satoshi Katsuno, Tatsuya Kitajiri, Shin-ichiro Koyanagi, Naoto Kawaguchi, Yasushi Onomoto, Koji Kato, Hiroki Yoneyama, Mitsutoshi Fujita, Takashi Tanaka, Nobuyuki |
author_sort | Hayashi, Yushi |
collection | PubMed |
description | Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL. |
format | Online Article Text |
id | pubmed-8629241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86292412021-11-30 Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis Hayashi, Yushi Suzuki, Hidenori Nakajima, Wataru Uehara, Ikuno Tanimura, Atsuko Himeda, Toshiki Koike, Satoshi Katsuno, Tatsuya Kitajiri, Shin-ichiro Koyanagi, Naoto Kawaguchi, Yasushi Onomoto, Koji Kato, Hiroki Yoneyama, Mitsutoshi Fujita, Takashi Tanaka, Nobuyuki PLoS One Research Article Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL. Public Library of Science 2021-11-29 /pmc/articles/PMC8629241/ /pubmed/34843580 http://dx.doi.org/10.1371/journal.pone.0260443 Text en © 2021 Hayashi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hayashi, Yushi Suzuki, Hidenori Nakajima, Wataru Uehara, Ikuno Tanimura, Atsuko Himeda, Toshiki Koike, Satoshi Katsuno, Tatsuya Kitajiri, Shin-ichiro Koyanagi, Naoto Kawaguchi, Yasushi Onomoto, Koji Kato, Hiroki Yoneyama, Mitsutoshi Fujita, Takashi Tanaka, Nobuyuki Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis |
title | Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis |
title_full | Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis |
title_fullStr | Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis |
title_full_unstemmed | Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis |
title_short | Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis |
title_sort | virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by trail-induced necroptosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629241/ https://www.ncbi.nlm.nih.gov/pubmed/34843580 http://dx.doi.org/10.1371/journal.pone.0260443 |
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