학술논문
Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies
Document Type
Original Paper
Author
Source
The EMBO Journal. 43(7):1135-1163
Subject
Language
English
ISSN
1460-2075
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.
Synopsis: Dysregulated immune responses lead to excessive inflammation in severe COVID-19, but the associated mechanisms and their regulation remain unclear. This study shows that in response to SARS-CoV-2 infection, the complement system induces innate and adaptive immune responses that can be countered by anti-SARS-CoV-2 antibodies.Complement-opsonized SARS-CoV-2 activates dendritic cells via binding to the CD11b/CR3 and CD11c/CR4 receptors.Complement-opsonized SARS-CoV-2 induces type-I interferon and pro-inflammatory cytokine responses by dendritic cells.Patient serum or monoclonal anti-SARS-CoV-2 antibodies attenuate complement-induced immune responses.Antibody-mediated suppression of the immune responses depends on the FcγRII antibody receptor of dendritic cells.
Patient serum or monoclonal antibodies against SARS-CoV-2 block type-I interferon and pro-inflammatory cytokine responses elicited by complement-opsonized SARS-CoV-2.
Synopsis: Dysregulated immune responses lead to excessive inflammation in severe COVID-19, but the associated mechanisms and their regulation remain unclear. This study shows that in response to SARS-CoV-2 infection, the complement system induces innate and adaptive immune responses that can be countered by anti-SARS-CoV-2 antibodies.Complement-opsonized SARS-CoV-2 activates dendritic cells via binding to the CD11b/CR3 and CD11c/CR4 receptors.Complement-opsonized SARS-CoV-2 induces type-I interferon and pro-inflammatory cytokine responses by dendritic cells.Patient serum or monoclonal anti-SARS-CoV-2 antibodies attenuate complement-induced immune responses.Antibody-mediated suppression of the immune responses depends on the FcγRII antibody receptor of dendritic cells.
Patient serum or monoclonal antibodies against SARS-CoV-2 block type-I interferon and pro-inflammatory cytokine responses elicited by complement-opsonized SARS-CoV-2.