Recombinant SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Stimulate Release of Different Pro-Inflammatory Mediators via Activation of Distinct Receptors on Human Microglia Cells
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
SARS-CoV-2 infects cells via its spike (S) protein binding to its surface receptor angiotensin converting enzyme 2 (ACE2) on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that SARS-CoV-2 infection produces neuroinflammation associated with neurological, neuropsychiatric, and cognitive symptoms persists well past the resolution of the infection, known as post-COVID-19 sequalae or long-COVID. The neuroimmune mechanism(s) involved in long-COVID have not been adequately characterized. In this study, we show that recombinant SARS-CoV-2 full-length S protein stimulates release of pro-inflammatory IL-1b, CXCL8, IL-6, and MMP-9 from cultured human microglia via TLR4 receptor activation. Instead, recombinant receptor-binding domain (RBD) stimulates release of TNF-α, IL-18, and S100B via ACE2 signaling. These results provide evidence that SARS-CoV-2 spike protein contributes to neuroinflammation through different mechanisms that may be involved in CNS pathologies associated with long-COVID.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
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| Enthalten in: |
Molecular neurobiology - 60(2023), 11 vom: 21. Nov., Seite 6704-6714 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tsilioni, Irene [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 23.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12035-023-03493-7 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a SARS-CoV-2 infects cells via its spike (S) protein binding to its surface receptor angiotensin converting enzyme 2 (ACE2) on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that SARS-CoV-2 infection produces neuroinflammation associated with neurological, neuropsychiatric, and cognitive symptoms persists well past the resolution of the infection, known as post-COVID-19 sequalae or long-COVID. The neuroimmune mechanism(s) involved in long-COVID have not been adequately characterized. In this study, we show that recombinant SARS-CoV-2 full-length S protein stimulates release of pro-inflammatory IL-1b, CXCL8, IL-6, and MMP-9 from cultured human microglia via TLR4 receptor activation. Instead, recombinant receptor-binding domain (RBD) stimulates release of TNF-α, IL-18, and S100B via ACE2 signaling. These results provide evidence that SARS-CoV-2 spike protein contributes to neuroinflammation through different mechanisms that may be involved in CNS pathologies associated with long-COVID | ||
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