Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2.
Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2.
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DOI：
10.1038/s41467-021-27318-0
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发表时间：
2021-12-07
影响因子：
16.6
通讯作者：
Duncan CJA
中科院分区：
文献类型：
--
作者：
Hatton CF;Botting RA;Dueñas ME;Haq IJ;Verdon B;Thompson BJ;Spegarova JS;Gothe F;Stephenson E;Gardner AI;Murphy S;Scott J;Garnett JP;Carrie S;Powell J;Khan CMA;Huang L;Hussain R;Coxhead J;Davey T;Simpson AJ;Haniffa M;Hambleton S;Brodlie M;Ward C;Trost M;Reynolds G;Duncan CJA
鼻上皮是SARS-CoV-2的一个可能的进入点，是发病和传播的部位，并可能启动宿主对SARS-CoV-2的反应。抗病毒干扰素（IFN）应答对SARS-CoV-2的结局至关重要。然而，人们对SARS-CoV-2与该组织中的先天免疫之间的相互作用知之甚少。在这里，我们应用单细胞RNA测序和蛋白质组学的原代细胞模型的人鼻上皮细胞分化的气液界面。SARS-CoV-2表现出对鼻上皮细胞类型的广泛嗜性。宿主反应主要由I型和III型干扰素和干扰素刺激的基因产物控制。这种反应相对于病毒基因表达和与其他呼吸道病毒相比明显延迟发作。然而，一旦建立，旁分泌IFN应答开始影响SARS-CoV-2复制。当在感染前提供时，重组IFNβ或IFNλ1诱导有效的抗病毒状态，有效地限制SARS-CoV-2病毒复制，保持上皮屏障完整性。这些数据表明，IFN-I/III对SARS-CoV-2的反应起始于鼻气道，并表明经鼻递送重组IFN是一种潜在的化学预防策略。SARS-CoV-2感染后上皮细胞的天然免疫应答尚未完全了解。在这里，作者使用人气液界面培养，并显示与其他呼吸道病毒相比，SARS-CoV-2感染后单细胞转录变化和延迟的I型干扰素反应。
The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we apply single-cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrates widespread tropism for nasal epithelial cell types. The host response is dominated by type I and III IFNs and interferon-stimulated gene products. This response is notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response begins to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFNβ or IFNλ1 induces an efficient antiviral state that potently restricts SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data imply that the IFN-I/III response to SARS-CoV-2 initiates in the nasal airway and suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy. The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses.
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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：
10.1074/jbc.ac120.013788
发表时间：
2020-10-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Felgenhauer U;Schoen A;Gad HH;Hartmann R;Schaubmar AR;Failing K;Drosten C;Weber F
通讯作者：
Weber F
影响因子：
6.4
作者：
Cardoso RS;Tavares LA;Jesus BLS;Criado MF;de Carvalho AN;Souza JP;Bedi S;de Souza MM;Silva ML;Lanfredi GP;Vitti BC;Scudero OB;Faça VM;Ono A;Ventura AM;daSilva LLP;Arruda E
通讯作者：
Arruda E
影响因子：
56.9
作者：
Broggi, Achille;Ghosh, Sreya;Zanoni, Ivan
通讯作者：
Zanoni, Ivan
SARS-COV-2和382-NT缺失分离株缺乏ORF8的人类鼻上皮细胞的感染揭示了类似的病毒动力学和宿主的转录谱。
影响因子：
6.7
作者：
Gamage AM;Tan KS;Chan WOY;Liu J;Tan CW;Ong YK;Thong M;Andiappan AK;Anderson DE;Wang Y;Wang LF
通讯作者：
Wang LF