Baricitinib attenuates the proinflammatory phase of COVID-19 driven by lung-infiltrating monocytes.
Baricitinib attenuates the proinflammatory phase of COVID-19 driven by lung-infiltrating monocytes.
复制标题
baritodinib减弱了由肺部膨胀单核细胞驱动的COVID-19的促炎阶段。
DOI：
10.1016/j.celrep.2022.110945
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发表时间：
2022-06-14
期刊：
影响因子：
8.8
通讯作者：
Tirouvanziam, Rabindra
中科院分区：
文献类型：
--
作者：
Dobosh, Brian;Zandi, Keivan;Giraldo, Diego Moncada;Goh, Shu Ling;Musall, Kathryn;Aldeco, Milagros;LeCher, Julia;Giacalone, Vincent D.;Yang, Junkai;Eddins, Devon J.;Bhasin, Manoj;Ghosn, Eliver;Sukhatme, Vikas;Schinazi, Raymond F.;Tirouvanziam, Rabindra
SARS-CoV-2感染者在最初的病毒复制过程中通常没有症状，但在病毒消退和单核细胞渗入呼吸道后可能会出现严重的免疫病理变化。在重症新冠肺炎患者的支气管肺泡灌洗液中，单核细胞表达炎症介质，并含有SARS-CoV-2转录本。我们利用人类小气道感染和炎症模型，在该模型中，初级血液单核细胞通过SARS-CoV-2感染的肺上皮细胞转移，以表征病毒负荷、基因表达以及上皮细胞和单核细胞分泌的炎症介质。在这个模型中，肺浸润性单核细胞从上皮细胞感染SARS-CoV-2，并上调炎症介质的表达和分泌，这反映了体内的数据。联合使用巴利替尼(Janus Kinase Inhibitor)和雷米西韦(Remsivir)可增强SARS-CoV-2阳性单核细胞的抗病毒信号和病毒清除，同时减少与急性呼吸窘迫综合征相关的嗜中性粒细胞介质的分泌。这些发现突显了肺浸润性单核细胞在新冠肺炎发病机制中的作用及其作为治疗靶点的重要性。Dobosh等人。概述SARS-CoV-2感染和随后由血液单核细胞进入肺的炎症在人类小气道模型中。肺招募的单核细胞从感染的上皮细胞感染SARS-CoV-2，但不能传播病毒。免疫调节药物巴利西尼促进单核细胞中的抗病毒信号，从而增强SARS-CoV-2的清除。
SARS-CoV-2-infected subjects are generally asymptomatic during initial viral replication but may suffer severe immunopathology after the virus has receded and monocytes have infiltrated the airways. In bronchoalveolar lavage fluid from severe COVID-19 patients, monocytes express mRNA encoding inflammatory mediators and contain SARS-CoV-2 transcripts. We leverage a human small airway model of infection and inflammation, whereby primary blood monocytes transmigrate across SARS-CoV-2-infected lung epithelium to characterize viral burden, gene expression, and inflammatory mediator secretion by epithelial cells and monocytes. In this model, lung-infiltrating monocytes acquire SARS-CoV-2 from the epithelium and upregulate expression and secretion of inflammatory mediators, mirroring in vivo data. Combined use of baricitinib (Janus kinase inhibitor) and remdesivir (nucleoside analog) enhances antiviral signaling and viral clearance by SARS-CoV-2-positive monocytes while decreasing secretion of proneutrophilic mediators associated with acute respiratory distress syndrome. These findings highlight the role of lung-infiltrating monocytes in COVID-19 pathogenesis and their importance as a therapeutic target. Dobosh et al. recapitulate infection by SARS-CoV-2 and subsequent inflammation by blood monocytes entering the lung in a human small airway model. Lung-recruited monocytes acquire SARS-CoV-2 from the infected epithelium but are unable to propagate virus. The immunomodulatory drug baricitinib promotes antiviral signaling in monocytes, which enhances clearance of SARS-CoV-2.
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影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
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：
--
作者：
Dobosh B;Giacalone VD;Margaroli C;Tirouvanziam R
通讯作者：
Tirouvanziam R
DOI：
10.3390/pathogens10091105
发表时间：
2021-08-30
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Li M;Zhang Y;Lu J;Li L;Gao H;Ma C;Dai E;Wei L
通讯作者：
Wei L
影响因子：
5.6
作者：
Ford BD;Moncada Giraldo D;Margaroli C;Giacalone VD;Brown MR;Peng L;Tirouvanziam R
通讯作者：
Tirouvanziam R