Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies
© 2024. The Author(s)..
Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
The EMBO journal - 43(2024), 7 vom: 28. Apr., Seite 1135-1163 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bermejo-Jambrina, Marta [VerfasserIn] |
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| Links: |
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| Themen: |
9007-36-7 |
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| Anmerkungen: |
Date Completed 04.04.2024 Date Revised 12.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s44318-024-00061-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369084810 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Complement | |
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| 650 | 4 | |a SARS-CoV-2 | |
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| 700 | 1 | |a van Hamme, John L |e verfasserin |4 aut | |
| 700 | 1 | |a Wilflingseder, Doris |e verfasserin |4 aut | |
| 700 | 1 | |a de Bree, Godelieve |e verfasserin |4 aut | |
| 700 | 1 | |a Prins, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a de Jong, Menno |e verfasserin |4 aut | |
| 700 | 1 | |a Nieuwkerk, Pythia |e verfasserin |4 aut | |
| 700 | 1 | |a van Gils, Marit J |e verfasserin |4 aut | |
| 700 | 1 | |a Kootstra, Neeltje A |e verfasserin |4 aut | |
| 700 | 1 | |a Geijtenbeek, Teunis Bh |e verfasserin |4 aut | |
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