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Статья
SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself
2021
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.
Цитирование
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Версии
- 1. Version of Record от 2021-12-01
Метаданные
Название журнала
- Nature Communications
Том
- 12
Выпуск
- 1
Финансирующая организация
- H2020 European Research Council
Номер гранта
- ERC-2010-AdG.20100317 Grant 268978
Тип документа
- journal article
Тип лицензии Creative Commons
- CC BY
Правовой статус документа
- Свободная лицензия
Источник
- scopus
