{"title":"Circulating extracellular vesicles from severe COVID-19 patients induce lung inflammation.","authors":"Huifeng Qian, Ruoxi Zang, Ruoyang Zhang, Guoping Zheng, Guanguan Qiu, Jianbiao Meng, Jiangmei Wang, Jie Xia, Ruoqiong Huang, Zhenkai Le, Qiang Shu, Jianguo Xu","doi":"10.1128/msphere.00764-24","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>in vitro</i>, 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 <i>in vivo</i>. 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.</p><p><strong>Importance: </strong>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 <i>in vivo</i>. <i>In vitro</i> 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.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0076424"},"PeriodicalIF":3.7000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580465/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"mSphere","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/msphere.00764-24","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
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.
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.