Single-cell multi-omics analysis of the immune response in COVID-19.
Single-cell multi-omics analysis of the immune response in COVID-19.
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DOI：
10.1038/s41591-021-01329-2
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发表时间：
2021-05
期刊：
影响因子：
82.9
通讯作者：
Haniffa M
中科院分区：
文献类型：
--
作者：
Stephenson E;Reynolds G;Botting RA;Calero-Nieto FJ;Morgan MD;Tuong ZK;Bach K;Sungnak W;Worlock KB;Yoshida M;Kumasaka N;Kania K;Engelbert J;Olabi B;Spegarova JS;Wilson NK;Mende N;Jardine L;Gardner LCS;Goh I;Horsfall D;McGrath J;Webb S;Mather MW;Lindeboom RGH;Dann E;Huang N;Polanski K;Prigmore E;Gothe F;Scott J;Payne RP;Baker KF;Hanrath AT;Schim van der Loeff ICD;Barr AS;Sanchez-Gonzalez A;Bergamaschi L;Mescia F;Barnes JL;Kilich E;de Wilton A;Saigal A;Saleh A;Janes SM;Smith CM;Gopee N;Wilson C;Coupland P;Coxhead JM;Kiselev VY;van Dongen S;Bacardit J;King HW;Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration;Rostron AJ;Simpson AJ;Hambleton S;Laurenti E;Lyons PA;Meyer KB;Nikolić MZ;Duncan CJA;Smith KGC;Teichmann SA;Clatworthy MR;Marioni JC;Göttgens B;Haniffa M
对人类血液免疫细胞的分析可以深入了解对病毒感染的协调反应，例如导致 2019 年冠状病毒病 (COVID-19) 的严重急性呼吸综合征冠状病毒 2。我们对来自 130 名不同严重程度的 COVID-19 患者的横断面队列中的 780,000 多个外周血单核细胞进行了单细胞转录组、表面蛋白质组以及 T 和 B 淋巴细胞抗原受体分析。我们发现了表达补体转录本 (CD16+C1QA/B/C+) 的非经典单核细胞的扩增，这些转录本会隔离血小板，并预计会补充 COVID-19 中的肺泡巨噬细胞池。早期，未定型的 CD34+ 造血干/祖细胞已准备好进行巨核细胞生成，伴随着巨核细胞定型祖细胞的扩大和血小板活化的增加。克隆性扩增的 CD8+ T 细胞以及 CD8+ 效应 T 细胞与效应记忆 T 细胞的比率增加是严重疾病的特征，而循环滤泡辅助 T 细胞则伴有轻度疾病。我们观察到，尽管浆母细胞和浆细胞总体扩张，但有症状的疾病中 IgA2 相对减少。我们的研究强调了导致 COVID-19 发病机制的协调免疫反应，并揭示了可作为治疗目标的离散细胞成分。对 COVID-19 患者血液样本的转录组学和蛋白质组学分析揭示了与疾病严重程度存在差异相关的免疫细胞和造血祖细胞的变化。
Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy. Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.
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危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
DOI：
10.1073/pnas.1417683112
发表时间：
2015-02-24
影响因子：
11.1
作者：
Gadala-Maria, Daniel;Yaari, Gur;Kleinstein, Steven H.
通讯作者：
Kleinstein, Steven H.
影响因子：
32.4
作者：
Evren, Elza;Ringqvist, Emma;Willinger, Tim
通讯作者：
Willinger, Tim
影响因子：
32.4
作者：
Boothby M;Rickert RC
通讯作者：
Rickert RC