SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.
SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.
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DOI：
10.1038/s41467-021-22210-3
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发表时间：
2021-03-30
影响因子：
16.6
通讯作者：
Mashreghi MF
中科院分区：
文献类型：
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作者：
Ferreira-Gomes M;Kruglov A;Durek P;Heinrich F;Tizian C;Heinz GA;Pascual-Reguant A;Du W;Mothes R;Fan C;Frischbutter S;Habenicht K;Budzinski L;Ninnemann J;Jani PK;Guerra GM;Lehmann K;Matz M;Ostendorf L;Heiberger L;Chang HD;Bauherr S;Maurer M;Schönrich G;Raftery M;Kallinich T;Mall MA;Angermair S;Treskatsch S;Dörner T;Corman VM;Diefenbach A;Volk HD;Elezkurtaj S;Winkler TH;Dong J;Hauser AE;Radbruch H;Witkowski M;Melchers F;Radbruch A;Mashreghi MF
严重COVID-19的发病机制反映了对SARS-CoV-2的免疫反应效率低下。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患者的适应性免疫反应的动态。在对SARS-CoV-2刺突蛋白应答的血清转化之前，外周浆母细胞显示1型干扰素诱导的基因表达特征;然而，在血清转化之后，浆母细胞失去该特征，而是表达由IL-21和TGF-β诱导的基因特征，并且主要产生IgG 1和IgA 1。在COVID-19患者的持续免疫反应中，浆母细胞转向表达IgA 2，从而反映了TGF-β的指示。尽管浆母细胞继续存在于血液中，但在死亡的COVID-19患者的肺部中未发现浆母细胞，患者IgA 2也不与SARS-CoV-2的优势抗原结合。因此，我们的研究结果表明，在严重的COVID-19中，SARS-CoV-2触发了一种由TGF-β指导的慢性免疫反应，并分散了自身的注意力。目前对SARS-CoV-2诱导的体液免疫机制的认识尚不清楚。在这里，作者分析了单细胞水平的B细胞反应，发现在严重的COVID-19患者中，浆母细胞从IFN转变为TGFβ指令，以产生对主要SARS-CoV-2抗原不特异的伊加抗体。
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. Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGFβ instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
DOI：
10.1186/s42358-020-00151-7
发表时间：
2020-09-22
期刊：
Advances in rheumatology (London, England)
影响因子：
--
作者：
Bordallo B;Bellas M;Cortez AF;Vieira M;Pinheiro M
通讯作者：
Pinheiro M
影响因子：
4.4
作者：
ISLAM, KB;NILSSON, L;SMITH, CIE
通讯作者：
SMITH, CIE
影响因子：
7.3
作者：
He, L.;Ding, Y.;Jiang, S.
通讯作者：
Jiang, S.
影响因子：
16.6
作者：
Vu Van D;Beier KC;Pietzke LJ;Al Baz MS;Feist RK;Gurka S;Hamelmann E;Kroczek RA;Hutloff A
通讯作者：
Hutloff A