Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.
Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.
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DOI：
10.1016/j.molcel.2022.04.033
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发表时间：
2022-07-07
期刊：
影响因子：
16
通讯作者：
Meunier, Etienne
中科院分区：
文献类型：
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作者：
Planes, Remi;Pinilla, Miriam;Santoni, Karin;Hessel, Audrey;Passemar, Charlotte;Lay, Kenneth;Paillette, Perrine;Valadao, Ana-Luiza Chaves;Robinson, Kim Samirah;Bastard, Paul;Lam, Nathaniel;Fadrique, Ricardo;Rossi, Ida;Pericat, David;Bagayoko, Salimata;Leon-Icaza, Stephen Adonai;Rombouts, Yoann;Perouzel, Eric;Tiraby, Michele;Zhang, Qian;Cicuta, Pietro;Jouanguy, Emmanuelle;Neyrolles, Olivier;Bryant, Clare E.;Floto, Andres R.;Goujon, Caroline;Lei, Franklin Zhong;Martin-Blondel, Guillaume;Silva, Stein;Casanova, Jean-Laurent;Cougoule, Celine;Reversade, Bruno;Marcoux, Julien;Ravet, Emmanuel;Meunier, Etienne
在感染SARS-CoV-2的患者中观察到的炎症反应表明，炎症体是促炎症的细胞内复合体，调节感染的各个步骤。肺上皮细胞表达炎症小体形成感受器，构成SARS-CoV-2的主要进入门。在这里，我们描述了NLRP1炎症组在人肺上皮细胞中检测SARS-CoV-2感染。具体地说，人类NLRP1在Q333位点被多个冠状病毒3CL蛋白酶切割，从而触发炎症体组装和细胞死亡，并限制感染性病毒颗粒的产生。对NLRP1相关途径的分析揭示，3CL蛋白酶也可以使嗜热症执行者Gasdermin D(GSDMD)失活。随后，caspase-3和GSDME促进交替的细胞下垂。最后，对因抗I型干扰素(IFN)自身抗体或先天错误而导致重症肺炎的新冠肺炎患者血浆中的下垂标志物的分析突出了GSDME/Caspase-3作为疾病严重程度的潜在标志物。总体而言，我们的发现确定NLRP1是肺上皮细胞中SARS-CoV-2感染的感受器。PlaneèS等人。鉴定人NLRP1为SARS-CoV2 3CL蛋白酶的免疫感受器。
Inflammation observed in SARS-CoV-2-infected patients suggests that inflammasomes, proinflammatory intracellular complexes, regulate various steps of infection. Lung epithelial cells express inflammasome-forming sensors and constitute the primary entry door of SARS-CoV-2. Here, we describe that the NLRP1 inflammasome detects SARS-CoV-2 infection in human lung epithelial cells. Specifically, human NLRP1 is cleaved at the Q333 site by multiple coronavirus 3CL proteases, which triggers inflammasome assembly and cell death and limits the production of infectious viral particles. Analysis of NLRP1-associated pathways unveils that 3CL proteases also inactivate the pyroptosis executioner Gasdermin D (GSDMD). Subsequently, caspase-3 and GSDME promote alternative cell pyroptosis. Finally, analysis of pyroptosis markers in plasma from COVID-19 patients with characterized severe pneumonia due to autoantibodies against, or inborn errors of, type I interferons (IFNs) highlights GSDME/caspase-3 as potential markers of disease severity. Overall, our findings identify NLRP1 as a sensor of SARS-CoV-2 infection in lung epithelia. Planès et al. identify human NLRP1 as an immune sensor of SARS-CoV2 3CL protease.
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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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：
10.1038/s41577-021-00522-1
发表时间：
2021-04
期刊：
Nature reviews. Immunology
影响因子：
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作者：
Carvalho T;Krammer F;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
56.9
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Bauernfried, Stefan;Scherr, Matthias J.;Hornung, Veit
通讯作者：
Hornung, Veit
影响因子：
56.9
作者：
Anand, K;Ziebuhr, J;Hilgenfeld, R
通讯作者：
Hilgenfeld, R
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通讯作者：
Jacks, Tyler