6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice
Sialic acids are terminal sugars of the cellular glycocalyx and are highly abundant in the nervous tissue. Sialylation is sensed by the innate immune system and acts as an inhibitory immune checkpoint. Aminoglycoside antibiotics such as neomycin have been shown to activate tissue macrophages and ind...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1264060/full |
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| author | Tawfik Abou Assale Thomas Kuenzel Tamara Schink Anahita Shahraz Harald Neumann Christine Klaus |
| author_facet | Tawfik Abou Assale Thomas Kuenzel Tamara Schink Anahita Shahraz Harald Neumann Christine Klaus |
| author_sort | Tawfik Abou Assale |
| collection | DOAJ |
| description | Sialic acids are terminal sugars of the cellular glycocalyx and are highly abundant in the nervous tissue. Sialylation is sensed by the innate immune system and acts as an inhibitory immune checkpoint. Aminoglycoside antibiotics such as neomycin have been shown to activate tissue macrophages and induce ototoxicity. In this study, we investigated the systemic subcutaneous application of the human milk oligosaccharide 6’-sialyllactose (6SL) as a potential therapy for neomycin-induced ototoxicity in postnatal mice. Repeated systemic treatment of mice with 6SL ameliorated neomycin-induced hearing loss and attenuated neomycin-triggered macrophage activation in the cochlear spiral ganglion. In addition, 6SL reversed the neomycin-mediated increase in gene transcription of the pro-inflammatory cytokine interleukin-1β (Il-1b) and the apoptotic/inflammatory kinase Pik3cd in the inner ear. Interestingly, neomycin application also increased the transcription of desialylating enzyme neuraminidase 3 (Neu3) in the inner ear. In vitro, we confirmed that treatment with 6SL had anti-inflammatory, anti-phagocytic, and neuroprotective effects on cultured lipopolysaccharide-challenged human THP1-macrophages. Thus, our data demonstrated that treatment with 6SL has anti-inflammatory and protective effects against neomycin-mediated macrophage activation and ototoxicity. |
| first_indexed | 2024-03-09T02:04:38Z |
| format | Article |
| id | doaj.art-5cd597601eca4746ad0e505fa58496ea |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T02:04:38Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5cd597601eca4746ad0e505fa58496ea2023-12-07T20:56:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.126406012640606’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible miceTawfik Abou Assale0Thomas Kuenzel1Tamara Schink2Anahita Shahraz3Harald Neumann4Christine Klaus5Neural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, GermanyAuditory Neurophysiology, Department of Chemosensation, Institute for Biology II, RWTH Aachen University, Aachen, GermanyNeural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, GermanyNeural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, GermanyNeural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, GermanyNeural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, GermanySialic acids are terminal sugars of the cellular glycocalyx and are highly abundant in the nervous tissue. Sialylation is sensed by the innate immune system and acts as an inhibitory immune checkpoint. Aminoglycoside antibiotics such as neomycin have been shown to activate tissue macrophages and induce ototoxicity. In this study, we investigated the systemic subcutaneous application of the human milk oligosaccharide 6’-sialyllactose (6SL) as a potential therapy for neomycin-induced ototoxicity in postnatal mice. Repeated systemic treatment of mice with 6SL ameliorated neomycin-induced hearing loss and attenuated neomycin-triggered macrophage activation in the cochlear spiral ganglion. In addition, 6SL reversed the neomycin-mediated increase in gene transcription of the pro-inflammatory cytokine interleukin-1β (Il-1b) and the apoptotic/inflammatory kinase Pik3cd in the inner ear. Interestingly, neomycin application also increased the transcription of desialylating enzyme neuraminidase 3 (Neu3) in the inner ear. In vitro, we confirmed that treatment with 6SL had anti-inflammatory, anti-phagocytic, and neuroprotective effects on cultured lipopolysaccharide-challenged human THP1-macrophages. Thus, our data demonstrated that treatment with 6SL has anti-inflammatory and protective effects against neomycin-mediated macrophage activation and ototoxicity.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1264060/fullneuroinflammationsialylation6’-sialyllactoseneomycinhearing lossmacrophages |
| spellingShingle | Tawfik Abou Assale Thomas Kuenzel Tamara Schink Anahita Shahraz Harald Neumann Christine Klaus 6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice Frontiers in Immunology neuroinflammation sialylation 6’-sialyllactose neomycin hearing loss macrophages |
| title | 6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice |
| title_full | 6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice |
| title_fullStr | 6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice |
| title_full_unstemmed | 6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice |
| title_short | 6’-sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice |
| title_sort | 6 sialyllactose ameliorates the ototoxic effects of the aminoglycoside antibiotic neomycin in susceptible mice |
| topic | neuroinflammation sialylation 6’-sialyllactose neomycin hearing loss macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1264060/full |
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