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严重 COVID-19 中的 SARS-CoV-2 诱导 TGF-β 主导的慢性免疫反应，但不针对自身。

SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.

机构信息

Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.

Belozersky Institute of Physico-Chemical Biology and Biological Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia.

出版信息

Nat Commun. 2021 Mar 30;12(1):1961. doi: 10.1038/s41467-021-22210-3.

DOI:10.1038/s41467-021-22210-3
PMID:33785765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8010106/
Abstract

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.

摘要

严重 COVID-19 的发病机制反映了对 SARS-CoV-2 的低效免疫反应。在这里，我们在单细胞水平上分析了流出到血液中的浆母细胞，以研究需要重症监护的 COVID-19 患者适应性免疫反应的动力学。在针对 SARS-CoV-2 刺突蛋白产生血清转化之前，外周浆母细胞表现出 I 型干扰素诱导的基因表达特征；然而，在血清转化之后，浆母细胞失去了这种特征，表达由 IL-21 和 TGF-β诱导的基因特征，并主要产生 IgG1 和 IgA1。在来自 COVID-19 患者的持续免疫反应中，浆母细胞转向 IgA2 的表达，从而反映了 TGF-β 的指令。尽管浆母细胞继续存在于血液中，但在已故 COVID-19 患者的肺部中未发现浆母细胞，并且患者的 IgA2 也不与 SARS-CoV-2 的主要抗原结合。因此，我们的结果表明，在严重的 COVID-19 中，SARS-CoV-2 引发了由 TGF-β指导的慢性免疫反应，并且摆脱了自身。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/9ed29afd6412/41467_2021_22210_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/ff979b81cdfe/41467_2021_22210_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/0ec38faaabd4/41467_2021_22210_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/1d0689c53713/41467_2021_22210_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/9ed29afd6412/41467_2021_22210_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/d5b8a713a8f2/41467_2021_22210_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/76322822b2fa/41467_2021_22210_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/d2ebda0c11e5/41467_2021_22210_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/ff979b81cdfe/41467_2021_22210_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/0ec38faaabd4/41467_2021_22210_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/1d0689c53713/41467_2021_22210_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b23/8010106/9ed29afd6412/41467_2021_22210_Fig7_HTML.jpg

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2
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3
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4
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6
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7
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8
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Nat Commun. 2020 May 22;11(1):2570. doi: 10.1038/s41467-020-16464-6.
9
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10
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