Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients.
Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients.
复制标题
炎性小体在应对SARS-CoV-2感染时被激活，并与患者的COVID-19严重程度相关。
DOI：
10.1084/jem.20201707
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Zamboni DS
中科院分区：
文献类型：
--
作者：
Rodrigues TS;de Sá KSG;Ishimoto AY;Becerra A;Oliveira S;Almeida L;Gonçalves AV;Perucello DB;Andrade WA;Castro R;Veras FP;Toller-Kawahisa JE;Nascimento DC;de Lima MHF;Silva CMS;Caetite DB;Martins RB;Castro IA;Pontelli MC;de Barros FC;do Amaral NB;Giannini MC;Bonjorno LP;Lopes MIF;Santana RC;Vilar FC;Auxiliadora-Martins M;Luppino-Assad R;de Almeida SCL;de Oliveira FR;Batah SS;Siyuan L;Benatti MN;Cunha TM;Alves-Filho JC;Cunha FQ;Cunha LD;Frantz FG;Kohlsdorf T;Fabro AT;Arruda E;de Oliveira RDR;Louzada-Junior P;Zamboni DS
这项工作表明，在体外和新冠肺炎患者中，炎症小体因受到SARS-CoV-2感染而被激活。中、重度新冠肺炎患者炎性小体的激活导致炎症反应加剧，影响疾病进展和临床预后。严重的新冠肺炎病例的特点是强烈的炎症过程，最终可能导致器官衰竭和患者死亡。NLRP3炎症体是一个分子平台，通过切割和激活包括活性半胱氨酸蛋白酶-1(Casp1p20)、IL-1β和IL-18在内的关键炎症分子来促进炎症。虽然炎症小体在新冠肺炎中的参与已经被高度推测，但炎症小体的激活和参与疾病转归的机制还不清楚。在这里，我们证明了NLRP3炎症小体是在应对SARS-CoV-2感染时被激活的，并且在新冠肺炎患者中是活跃的。以中、重度新冠肺炎患者为研究对象，尸检发现其外周血单核细胞和尸检组织中存在活跃的NLRP3炎症体。血清中炎症体衍生产物如Casp1p20和IL-18与新冠肺炎严重程度的标志物包括IL-6和LDH相关。此外，IL-18和Casp1p20水平升高与疾病严重程度和临床预后不良有关。我们的结果表明，炎性小体参与了疾病的病理生理过程，表明这些平台可能是疾病严重程度的标志和新冠肺炎的潜在治疗靶点。
This work shows that inflammasomes are activated in response to SARS-CoV-2 infection in vitro and in COVID-19 patients. Activation of inflammasomes in moderate and severe cases of COVID-19 contributes to the exacerbated inflammatory response, impacting disease progression and clinical outcome. Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.
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