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Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice
Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surfa...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597263/ https://www.ncbi.nlm.nih.gov/pubmed/28859161 http://dx.doi.org/10.1371/journal.ppat.1006599 |
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author | Almishaal, Ali A. Mathur, Pranav D. Hillas, Elaine Chen, Liting Zhang, Anne Yang, Jun Wang, Yong Yokoyama, Wayne M. Firpo, Matthew A. Park, Albert H. |
author_facet | Almishaal, Ali A. Mathur, Pranav D. Hillas, Elaine Chen, Liting Zhang, Anne Yang, Jun Wang, Yong Yokoyama, Wayne M. Firpo, Matthew A. Park, Albert H. |
author_sort | Almishaal, Ali A. |
collection | PubMed |
description | Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice. |
format | Online Article Text |
id | pubmed-5597263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55972632017-09-15 Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice Almishaal, Ali A. Mathur, Pranav D. Hillas, Elaine Chen, Liting Zhang, Anne Yang, Jun Wang, Yong Yokoyama, Wayne M. Firpo, Matthew A. Park, Albert H. PLoS Pathog Research Article Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice. Public Library of Science 2017-08-31 /pmc/articles/PMC5597263/ /pubmed/28859161 http://dx.doi.org/10.1371/journal.ppat.1006599 Text en © 2017 Almishaal et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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 Almishaal, Ali A. Mathur, Pranav D. Hillas, Elaine Chen, Liting Zhang, Anne Yang, Jun Wang, Yong Yokoyama, Wayne M. Firpo, Matthew A. Park, Albert H. Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
title | Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
title_full | Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
title_fullStr | Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
title_full_unstemmed | Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
title_short | Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
title_sort | natural killer cells attenuate cytomegalovirus-induced hearing loss in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597263/ https://www.ncbi.nlm.nih.gov/pubmed/28859161 http://dx.doi.org/10.1371/journal.ppat.1006599 |
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