Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.
Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.
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地塞米松调节严重的Covid-19中未成熟的中性粒细胞和干扰素编程。
DOI：
10.1038/s41591-021-01576-3
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发表时间：
2022-01
期刊：
影响因子：
82.9
通讯作者：
Biernaskie J
中科院分区：
文献类型：
--
作者：
Sinha S;Rosin NL;Arora R;Labit E;Jaffer A;Cao L;Farias R;Nguyen AP;de Almeida LGN;Dufour A;Bromley A;McDonald B;Gillrie MR;Fritzler MJ;Yipp BG;Biernaskie J
虽然对于宿主防御至关重要，但先天免疫细胞也是急性呼吸窘迫综合征（ARDS）的病理驱动因素。与其他呼吸道病原体引起的ARDS相比，2019冠状病毒病（COVID-19）ARDS期间的先天免疫动力学尚不清楚。此外，地塞米松在严重COVID-19期间的有益作用的潜在机制仍然难以捉摸。使用单细胞RNA测序和血浆蛋白质组学，我们发现，与细菌性ARDS相比，COVID-19与以干扰素（IFN）和前列腺素信号传导为特征的不同中性粒细胞状态的扩张有关。严重COVID-19期间的地塞米松影响循环中性粒细胞，改变IFN活性中性粒细胞，下调干扰素刺激基因并激活IL-1 R2+中性粒细胞。地塞米松还通过将中性粒细胞从信息接收者转变为信息提供者来扩增免疫抑制性未成熟中性粒细胞并重塑细胞相互作用。男性患者IFN活性中性粒细胞比例较高，激素诱导的未成熟中性粒细胞扩增优先，可能影响预后。我们的单细胞图谱（见“数据可用性”部分）定义了COVID-19富集的中性粒细胞状态和地塞米松作用的分子机制，以开发针对严重COVID-19的靶向免疫疗法。新的结果揭示了地塞米松作用的分子机制，支持其在严重COVID-19患者中的治疗益处。
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated genes and activated IL-1R2+ neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see ‘Data availability’ section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19. New results shed light on the molecular mechanisms of dexamethasone action, underlying its therapeutic benefit in patients with severe COVID-19.
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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
DOI：
10.15557/pimr.2020.0003
发表时间：
2020-01-01
影响因子：
3.6
作者：
通讯作者：
--
影响因子：
3.7
作者：
Brundin-Mather, Rebecca;Soo, Andrea;Stelfox, Henry T.
通讯作者：
Stelfox, Henry T.
影响因子：
16.6
作者：
Feng Z;Yu Q;Yao S;Luo L;Zhou W;Mao X;Li J;Duan J;Yan Z;Yang M;Tan H;Ma M;Li T;Yi D;Mi Z;Zhao H;Jiang Y;He Z;Li H;Nie W;Liu Y;Zhao J;Luo M;Liu X;Rong P;Wang W
通讯作者：
Wang W
影响因子：
9.3
作者：
Demichev V;Tober-Lau P;Lemke O;Nazarenko T;Thibeault C;Whitwell H;Röhl A;Freiwald A;Szyrwiel L;Ludwig D;Correia-Melo C;Aulakh SK;Helbig ET;Stubbemann P;Lippert LJ;Grüning NM;Blyuss O;Vernardis S;White M;Messner CB;Joannidis M;Sonnweber T;Klein SJ;Pizzini A;Wohlfarter Y;Sahanic S;Hilbe R;Schaefer B;Wagner S;Mittermaier M;Machleidt F;Garcia C;Ruwwe-Glösenkamp C;Lingscheid T;Bosquillon de Jarcy L;Stegemann MS;Pfeiffer M;Jürgens L;Denker S;Zickler D;Enghard P;Zelezniak A;Campbell A;Hayward C;Porteous DJ;Marioni RE;Uhrig A;Müller-Redetzky H;Zoller H;Löffler-Ragg J;Keller MA;Tancevski I;Timms JF;Zaikin A;Hippenstiel S;Ramharter M;Witzenrath M;Suttorp N;Lilley K;Mülleder M;Sander LE;PA-COVID-19 Study group;Ralser M;Kurth F
通讯作者：
Kurth F