Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses.
Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses.
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DOI：
10.3389/fimmu.2022.984553
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发表时间：
2022
影响因子：
7.3
通讯作者：
Yu, Xu G. G.
中科院分区：
文献类型：
--
作者：
Sun, Xiaoming;Gao, Ce;Zhao, Ke;Yang, Yanhui;Rassadkina, Yelizaveta;Fajnzylber, Jesse;Regan, James;Li, Jonathan Z. Z.;Lichterfeld, Mathias;Yu, Xu G. G.
SARS-CoV-2血浆病毒血症与COVID-19中的严重疾病和死亡相关。然而，病毒血症对血细胞免疫反应的影响仍不清楚。目前的研究全面检查了PBMC的转录特征，分别涉及T细胞、B细胞、NK细胞、单核细胞、髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC），这些细胞来自三个不同的组，包括患有中度（nM）或重度疾病且具有（vS）或不具有（nS）可检测的血浆病毒载量的个体。全转录组分析表明，所有七种免疫细胞亚群与疾病的严重程度相关，无论细胞类型如何。监督聚类分析表明，mDC和pDC基因签名可以区分疾病的严重程度。值得注意的是，vS组的转录特征在与DNA修复、E2 F靶点和G2 M检查点相关的途径中富集;相反，nM组的转录特征在干扰素应答中富集。此外，我们观察到干扰素应答的诱导受损，伴有不平衡的细胞内在免疫感应和严重疾病患者（nS和vS）的过度炎症反应。总之，我们的研究提供了对SARS-CoV-2感染的全身免疫反应的详细见解，并揭示了COVID-19患者七种主要免疫细胞的深刻变化。
SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.
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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：
5.7
作者：
Freitas RS;Crum TF;Parvatiyar K
通讯作者：
Parvatiyar K
影响因子：
6.4
作者：
Boumaza, Asma;Gay, Laetitia;Mege, Jean-Louis
通讯作者：
Mege, Jean-Louis
影响因子：
24.8
作者：
Lee, Jeong Seok;Park, Seongwan;Shin, Eui-Cheol
通讯作者：
Shin, Eui-Cheol
细胞衰老的机制：细胞周期停滞和衰老相关的分泌表型。
影响因子：
5.5
作者：
Kumari R;Jat P
通讯作者：
Jat P