Circulating extracellular vesicles from severe COVID-19 patients induce lung inflammation.

IF 3.7 2区 生物学 Q2 MICROBIOLOGY
mSphere Pub Date : 2024-10-30 DOI:10.1128/msphere.00764-24
Huifeng Qian, Ruoxi Zang, Ruoyang Zhang, Guoping Zheng, Guanguan Qiu, Jianbiao Meng, Jiangmei Wang, Jie Xia, Ruoqiong Huang, Zhenkai Le, Qiang Shu, Jianguo Xu
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引用次数: 0

Abstract

Circulating extracellular vesicles (EVs) have been associated with the development of COVID-19 due to their roles in viral infection, inflammatory response, and thrombosis. However, the direct induction of lung inflammation by circulating EVs from severe COVID-19 patients remains unknown. EVs were extracted from the plasma of severe COVID-19 patients admitted to intensive care and healthy controls. To study the effect of COVID-19 EVs on lung inflammation, mice were intratracheally instilled with EVs. To examine the proinflammatory effects of EVs in vitro, bone marrow-derived macrophages were treated with EVs. COVID-19 but not control EVs triggered lung inflammation, as assessed by total protein level, total cell count, neutrophil count, and levels of proinflammatory cytokines in the bronchoalveolar lavage. COVID-19 EVs also promoted M1 polarization of alveolar macrophages in vivo. Treatment of bone marrow-derived macrophages with COVID-19 EVs enhanced the M1 phenotype and augmented the production of IL-1β, IL-6, and TNF-α. In summary, circulating EVs from severe COVID-19 patients induce lung inflammation in mice. EVs could become a potential therapeutic target for alleviating lung injury in COVID-19.

Importance: Extracellular vesicles (EVs) have been reported to facilitate cytokine storm, coagulation, vascular dysfunction, and the spread of the virus in COVID-19. The direct role of circulating EVs from severe COVID-19 patients in lung injury remains unrecognized. Our study demonstrated that plasma EVs obtained from severe COVID-19 patients induced lung inflammation and polarization of alveolar macrophages in vivo. In vitro experiments also revealed the proinflammatory effects of COVID-19 EVs. The present study sheds fresh insight into the mechanisms of COVID-19-induced lung injury, highlighting EVs as a potential therapeutic target in combating the disease.

来自严重 COVID-19 患者的循环细胞外囊泡会诱发肺部炎症。
由于循环细胞外囊泡(EVs)在病毒感染、炎症反应和血栓形成中的作用,它们与 COVID-19 的发病有关。然而,严重COVID-19患者的循环EVs对肺部炎症的直接诱导作用仍然未知。研究人员从接受重症监护的重症 COVID-19 患者和健康对照组的血浆中提取了 EVs。为了研究 COVID-19 EVs 对肺部炎症的影响,给小鼠气管内灌注了 EVs。为了研究 EVs 在体外的促炎作用,用 EVs 处理骨髓衍生的巨噬细胞。根据支气管肺泡灌洗液中的总蛋白水平、总细胞数、中性粒细胞数和促炎细胞因子水平评估,COVID-19 而非对照组 EVs 会引发肺部炎症。COVID-19 EVs 还能促进体内肺泡巨噬细胞的 M1 极化。用 COVID-19 EVs 处理骨髓衍生巨噬细胞可增强 M1 表型,并增加 IL-1β、IL-6 和 TNF-α 的产生。总之,来自严重 COVID-19 患者的循环 EV 可诱导小鼠肺部炎症。EVs可能成为缓解COVID-19肺损伤的潜在治疗靶点:据报道,细胞外囊泡(EVs)可促进细胞因子风暴、凝血、血管功能障碍以及 COVID-19 病毒的传播。重症 COVID-19 患者的循环 EVs 在肺损伤中的直接作用仍未得到确认。我们的研究表明,从重症 COVID-19 患者体内获得的血浆 EV 可诱导肺部炎症和肺泡巨噬细胞的极化。体外实验也揭示了 COVID-19 EVs 的促炎作用。本研究揭示了COVID-19诱导肺损伤的新机制,强调了EVs是抗击该疾病的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
mSphere
mSphere Immunology and Microbiology-Microbiology
CiteScore
8.50
自引率
2.10%
发文量
192
审稿时长
11 weeks
期刊介绍: mSphere™ is a multi-disciplinary open-access journal that will focus on rapid publication of fundamental contributions to our understanding of microbiology. Its scope will reflect the immense range of fields within the microbial sciences, creating new opportunities for researchers to share findings that are transforming our understanding of human health and disease, ecosystems, neuroscience, agriculture, energy production, climate change, evolution, biogeochemical cycling, and food and drug production. Submissions will be encouraged of all high-quality work that makes fundamental contributions to our understanding of microbiology. mSphere™ will provide streamlined decisions, while carrying on ASM''s tradition for rigorous peer review.
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