Distribution of Immune Cells Including Macrophages in the Human Cochlea
Background: The human cochlea was earlier believed to lack capacity to mount specific immune responses. Recent studies established that the human cochlea holds macrophages. The cells appear to surveil, dispose of, and restore wasted cells to maintain tissue integrity. Macrophage activities are belie...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:c39e99e1fe8c4244a666b78fd4d445e12021-11-22T05:12:18ZDistribution of Immune Cells Including Macrophages in the Human Cochlea1664-229510.3389/fneur.2021.781702https://doaj.org/article/c39e99e1fe8c4244a666b78fd4d445e12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.781702/fullhttps://doaj.org/toc/1664-2295Background: The human cochlea was earlier believed to lack capacity to mount specific immune responses. Recent studies established that the human cochlea holds macrophages. The cells appear to surveil, dispose of, and restore wasted cells to maintain tissue integrity. Macrophage activities are believed to be the central elements in immune responses and could swiftly defuse invading microbes that enter via adjacent infection-prone areas. This review updates recent human studies in light of the current literature and adds information about chemokine gene expression.Materials and Methods: We analyzed surgically obtained human tissue using immunohistochemistry, confocal microscopy, and multichannel super-resolution structured illumination microscopy. The samples were considered representative of steady-state conditions. Antibodies against the ionized calcium-binding adaptor molecule 1 were used to identify the macrophages. CD68 and CD11b, and the major histocompatibility complex type II (MHCII) and CD4 and CD8 were analyzed. The RNAscope technique was used for fractalkine gene localization.Results: Many macrophages were found around blood vessels in the stria vascularis but not CD4 and CD8 lymphocytes. Amoeboid macrophages were identified in the spiral ganglion with surveilling “antennae” projecting against targeted cells. Synapse-like contacts were seen on spiral ganglion cell bodies richly expressing single CXC3CL gene transcripts. Branching neurite-like processes extended along central and peripheral axons. Active macrophages were occasionally found near degenerating hair cells. Some macrophage-interacting T lymphocytes were observed between the scala tympani wall and Rosenthal's canal. CD4 and CD8 cells were not found in the organ of Corti.Conclusions: The results indicate that the human cochlea is equipped with macrophages and potentially lymphocytes, suggesting both an innate and adaptive immune capacity. A rich expression of fractalkine gene transcripts in spiral ganglion neurons suggest an essential role for auditory nerve protection, as has been demonstrated experimentally. The findings provide further information on the important role of the immune machinery present in the human inner ear and its potential to carry adverse immune reactions, including cytotoxic and foreign body responses. The results can be used to form a rationale for therapies aiming to modulate these immune activities.Wei LiuNiklas Danckwardt-LillieströmAnneliese Schrott-FischerRudolf GlueckertHelge Rask-AndersenFrontiers Media S.A.articlehumancochleamacrophagesCX3CL1 genesRNA in situ hybridizationNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021) |
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human cochlea macrophages CX3CL1 genes RNA in situ hybridization Neurology. Diseases of the nervous system RC346-429 |
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human cochlea macrophages CX3CL1 genes RNA in situ hybridization Neurology. Diseases of the nervous system RC346-429 Wei Liu Niklas Danckwardt-Lillieström Anneliese Schrott-Fischer Rudolf Glueckert Helge Rask-Andersen Distribution of Immune Cells Including Macrophages in the Human Cochlea |
description |
Background: The human cochlea was earlier believed to lack capacity to mount specific immune responses. Recent studies established that the human cochlea holds macrophages. The cells appear to surveil, dispose of, and restore wasted cells to maintain tissue integrity. Macrophage activities are believed to be the central elements in immune responses and could swiftly defuse invading microbes that enter via adjacent infection-prone areas. This review updates recent human studies in light of the current literature and adds information about chemokine gene expression.Materials and Methods: We analyzed surgically obtained human tissue using immunohistochemistry, confocal microscopy, and multichannel super-resolution structured illumination microscopy. The samples were considered representative of steady-state conditions. Antibodies against the ionized calcium-binding adaptor molecule 1 were used to identify the macrophages. CD68 and CD11b, and the major histocompatibility complex type II (MHCII) and CD4 and CD8 were analyzed. The RNAscope technique was used for fractalkine gene localization.Results: Many macrophages were found around blood vessels in the stria vascularis but not CD4 and CD8 lymphocytes. Amoeboid macrophages were identified in the spiral ganglion with surveilling “antennae” projecting against targeted cells. Synapse-like contacts were seen on spiral ganglion cell bodies richly expressing single CXC3CL gene transcripts. Branching neurite-like processes extended along central and peripheral axons. Active macrophages were occasionally found near degenerating hair cells. Some macrophage-interacting T lymphocytes were observed between the scala tympani wall and Rosenthal's canal. CD4 and CD8 cells were not found in the organ of Corti.Conclusions: The results indicate that the human cochlea is equipped with macrophages and potentially lymphocytes, suggesting both an innate and adaptive immune capacity. A rich expression of fractalkine gene transcripts in spiral ganglion neurons suggest an essential role for auditory nerve protection, as has been demonstrated experimentally. The findings provide further information on the important role of the immune machinery present in the human inner ear and its potential to carry adverse immune reactions, including cytotoxic and foreign body responses. The results can be used to form a rationale for therapies aiming to modulate these immune activities. |
format |
article |
author |
Wei Liu Niklas Danckwardt-Lillieström Anneliese Schrott-Fischer Rudolf Glueckert Helge Rask-Andersen |
author_facet |
Wei Liu Niklas Danckwardt-Lillieström Anneliese Schrott-Fischer Rudolf Glueckert Helge Rask-Andersen |
author_sort |
Wei Liu |
title |
Distribution of Immune Cells Including Macrophages in the Human Cochlea |
title_short |
Distribution of Immune Cells Including Macrophages in the Human Cochlea |
title_full |
Distribution of Immune Cells Including Macrophages in the Human Cochlea |
title_fullStr |
Distribution of Immune Cells Including Macrophages in the Human Cochlea |
title_full_unstemmed |
Distribution of Immune Cells Including Macrophages in the Human Cochlea |
title_sort |
distribution of immune cells including macrophages in the human cochlea |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/c39e99e1fe8c4244a666b78fd4d445e1 |
work_keys_str_mv |
AT weiliu distributionofimmunecellsincludingmacrophagesinthehumancochlea AT niklasdanckwardtlilliestrom distributionofimmunecellsincludingmacrophagesinthehumancochlea AT annelieseschrottfischer distributionofimmunecellsincludingmacrophagesinthehumancochlea AT rudolfglueckert distributionofimmunecellsincludingmacrophagesinthehumancochlea AT helgeraskandersen distributionofimmunecellsincludingmacrophagesinthehumancochlea |
_version_ |
1718418185012641792 |