SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.
Adult
Aged
Aged, 80 and over
Antibodies, Viral
/ immunology
COVID-19
/ immunology
Female
Humans
Immunoglobulin A
/ immunology
Immunoglobulin G
/ immunology
Interleukins
/ immunology
Male
Middle Aged
Plasma Cells
/ immunology
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
Transforming Growth Factor beta
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 03 2021
30 03 2021
Historique:
received:
24
09
2020
accepted:
01
03
2021
entrez:
31
3
2021
pubmed:
1
4
2021
medline:
13
4
2021
Statut:
epublish
Résumé
The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.
Identifiants
pubmed: 33785765
doi: 10.1038/s41467-021-22210-3
pii: 10.1038/s41467-021-22210-3
pmc: PMC8010106
doi:
Substances chimiques
Antibodies, Viral
0
Immunoglobulin A
0
Immunoglobulin G
0
Interleukins
0
Spike Glycoprotein, Coronavirus
0
Transforming Growth Factor beta
0
spike protein, SARS-CoV-2
0
interleukin-21
MKM3CA6LT1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1961Subventions
Organisme : EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)
ID : ERDF 2014-2020, EFRE 1.8/11, Deutsches Rheuma-Forschungszentrum
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : COVID19-014 01KI2043A CoVER-Ab
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : ERC-2010-AdG.20100317 Grant 268978
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