Induction of MHC Class II Antigens on Cells of the Inner Ear

Gloddek, B.; Bodmer, Daniel; Brors, Dominik; Keithley, Elizabeth M.; Ryan, Allen F.

doi:10.1159/000066158

Cited by 14 publications

(11 citation statements)

References 26 publications

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“…First, MHC II expression is upregulated after acoustic trauma. This result is consistent with a previous observation that immune challenge is able to provoke cochlear immune cells to express MHC II (Gloddek et al, 2002). MHC II is an essential component of the antigen-presenting machinery, serving as a vehicle to transfer antigens to the cell surface.…”

Section: Discussionsupporting

confidence: 94%

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation

et al. 2015

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The immune response is an important component of the cochlear response to stress. As an important player in the cochlear immune system, the basilar membrane immune cells reside on the surface of the scala tympani side of the basilar membrane. At present, the immune cell properties in this region and their responses to stress are not well understood. Here, we investigated the functional role of these immune cells in the immune response to acoustic overstimulation. This study reveals that tissue macrophages are present in the entire length of the basilar membrane under steady-state conditions. Notably, these cells in the apical and the basal sections of the basilar membrane display distinct morphologies and immune protein expression patterns. Following acoustic trauma, monocytes infiltrate into the region of the basilar membrane, and the infiltrated cells transform into macrophages. While monocyte infiltration and transformation occur in both the apical and the basal sections of the basilar membrane, only the basal monocytes and macrophages display a marked increase in the expression of MHC II and CIITA, a MHC II production cofactor, suggesting the site-dependent activation of antigen-presenting function. Consistent with the increased expression of the antigen-presenting proteins, CD4+ T cells, the antigen-presenting partner, infiltrate into the region of the basilar membrane where antigen-presenting proteins are upregulated. Further pathological analyses revealed that the basal section of the cochlea displays a greater level of sensory cell damage, which is spatially correlated with the region of antigen-presenting activity. Together, these results suggest that the antigen-presenting function of the mononuclear phagocyte population is activated in response to acoustic trauma, which could bridge the innate immune response to adaptive immunity.

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Section: Discussionsupporting

confidence: 94%

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation

et al. 2015

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“…We previously demonstrated the activation of the antigen-presenting function in cochlear macrophages after acoustic injury, 7 which is consistent with a previous study of the induction of MHC II expression following immune challenge by sterile labyrinthitis in the cochlea. 34 Here, we demonstrated that the lack of Tlr4 function suppresses the noise-induced production of MHC II, suggesting that Tlr4 participates in noise-induced antigen-presentation activity. Notably, Tlr4 deficiency does not affect the internalization and proteolysis of antigen molecules by macrophages, as evidenced by the continued uptake and cellular processing of DQ-Ovalbumin.…”

Section: Discussionmentioning

confidence: 66%

Toll-like receptor 4 modulates the cochlear immune response to acoustic injury

et al. 2016

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Acoustic overstimulation traumatizes the cochlea, resulting in auditory dysfunction. As a consequence of acoustic injury, the immune system in the cochlea is activated, leading to the production of inflammatory mediators and the infiltration of immune cells. However, the molecular mechanisms responsible for initiating these immune responses remain unclear. Here, we investigate the functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that activates the innate immune system, in the regulation of cochlear responses to acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell viability under physiological conditions, but reduces the level of sensory cell damage and cochlear dysfunction after acoustic injury. Together, these findings suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction after acoustic injury. Acoustic injury provokes a site-dependent inflammatory response in both the organ of Corti and the tissues of the lateral wall and basilar membrane. Tlr4 deficiency affects these inflammatory responses in a site-dependent manner. In the organ of Corti, loss of Tlr4 function suppresses the production of interleukin 6 (Il6), a pro-inflammatory molecule, after acoustic injury. By contrast, the production of inflammatory mediators, including Il6, persists in the lateral wall and basilar membrane. In addition to immune molecules, Tlr4 knockout inhibits the expression of major histocompatibility complex class II, an antigen-presenting molecule, in macrophages, suggesting that Tlr4 participates in the antigen-presenting function of macrophages after acoustic trauma. Together, these results suggest that Tlr4 regulates multiple aspects of the immune response in the cochlea and contributes to cochlear pathogenesis after acoustic injury.

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“…In the event of acute sensory cell damage induced by ototoxicity, immune challenge or acoustic injury, a large number of undifferentiated monocytes from circulation expeditiously infiltrate into the cochlea (Hirose et al, 2005; Kaur et al, 2015; Okano et al, 2008; Shi, 2010; Tornabene et al, 2006; Yang et al, 2015). Therefore, infiltrated macrophages are the major executor for the immune activities, including phagocytosis of broken-down cellular material (Fredelius et al, 1990) and inflammatory molecule production (Fujioka et al, 2006; Gloddek et al, 2002; Tornabene et al, 2006; Yang et al, 2015). In contrast, in the event of chronic sensory cell degeneration, the immune response is fulfilled primarily by mature tissue macrophages.…”

Section: Discussionmentioning

confidence: 99%

Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae

et al. 2017

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In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status.

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Induction of MHC Class II Antigens on Cells of the Inner Ear

Cited by 14 publications

References 26 publications

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation

Toll-like receptor 4 modulates the cochlear immune response to acoustic injury

Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae

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