Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
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DOI：
10.1016/j.xcrm.2020.100146
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发表时间：
2020-12-22
期刊：
影响因子：
--
通讯作者：
Duivenvoorden R
中科院分区：
文献类型：
--
作者：
Rother N;Yanginlar C;Lindeboom RGH;Bekkering S;van Leent MMT;Buijsers B;Jonkman I;de Graaf M;Baltissen M;Lamers LA;Riksen NP;Fayad ZA;Mulder WJM;Hilbrands LB;Joosten LAB;Netea MG;Vermeulen M;van der Vlag J;Duivenvoorden R
正在研究羟氯喹对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的潜在预防作用，但其作用机制尚不清楚。 2019 年冠状病毒病 (COVID-19) 患者血液中的循环白细胞对 Toll 样受体配体的反应增强，表明其免疫力经过训练。通过分析用热灭活念珠菌调节的健康供体的外周血单核细胞的干扰素反应，可以在体外模拟经过训练的先天免疫。在该模型中，羟氯喹抑制这些先天免疫细胞对病毒样刺激和干扰素的反应。这与炎症相关基因的组蛋白 3 赖氨酸 27 乙酰化和组蛋白 3 赖氨酸 4 三甲基化的抑制、细胞脂质组的变化以及干扰素刺激基因的表达减少有关。我们的研究结果表明，羟氯喹会抑制体外训练有素的免疫力，这可能不利于患者针对 SARS-CoV-2 感染的抗病毒先天免疫反应。 COVID-19 患者的 PBMC 对 Toll 样受体配体的反应增强 使用念珠菌训练的 PBMC 在体外模拟训练后的免疫 羟氯喹抑制脂质组和组蛋白修饰的变化 羟氯喹抑制对干扰素和病毒刺激的训练反应 COVID-19 患者的外周血单核细胞 (PBMC) 对 Toll 样受体配体的反应增强，提示先天免疫重新编程。罗瑟等人。研究表明，羟氯喹可在体外抑制来自健康供体的经念珠菌训练的 PBMC 的干扰素反应，并阻止脂质组和组蛋白修饰的相关变化。
Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed Candida, trained innate immunity can be modeled in vitro. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity in vitro, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients. PBMCs of COVID-19 patients show increased responses to Toll-like receptor ligands Trained immunity is modeled in vitro using Candida-trained PBMCs Hydroxychloroquine inhibits changes in lipidome and histone modifications Hydroxychloroquine dampens the trained response to interferons and viral stimuli Peripheral blood mononuclear cells (PBMCs) of COVID-19 patients show increased responses to Toll-like receptor ligands, suggestive of innate immune reprogramming. Rother et al. show that hydroxychloroquine inhibits the interferon response of Candida-trained PBMCs from healthy donors in vitro and blocks associated changes in lipidome and histone modifications.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
影响因子：
158.5
作者：
Boulware, David R.;Pullen, Matthew F.;Hullsiek, Kathy H.
通讯作者：
Hullsiek, Kathy H.
影响因子：
24.8
作者：
Lee, Jeong Seok;Park, Seongwan;Shin, Eui-Cheol
通讯作者：
Shin, Eui-Cheol
影响因子：
--
作者：
Bekkering, Siroon;Blok, Bastiaan A.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.