Control of Complement-induced Inflammatory Responses to SARS-CoV-2 Infection by Anti-SARS-CoV-2 Antibodies

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2024 Feb 28

PMID 38418557

Authors

Marta Bermejo-Jambrina

Lieve Eh van der Donk

John L van Hamme

Doris Wilflingseder

Godelieve de Bree

Maria Prins

Menno de Jong

Pythia Nieuwkerk

Marit J van Gils

Neeltje A Kootstra

Teunis Bh Geijtenbeek

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis.

Gebetsberger L, Malekshahi Z, Teutsch A, Tajti G, Fontaine F, Marella N Emerg Microbes Infect. 2024; 13(1):2417868.

PMID: 39435487 PMC: 11520101. DOI: 10.1080/22221751.2024.2417868.

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