小鼠感染sars - cov -2后持续肺部炎症与肺T细胞增加有关

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Sophie Y. Guan, Patricia P. Ogger, Ana Farias, Minerva Garcia Martín, Joy Nakawesi, Olivia Bedard, Candice Baker, Nadia Rosenthal, Cecilia Johansson
{"title":"小鼠感染sars - cov -2后持续肺部炎症与肺T细胞增加有关","authors":"Sophie Y. Guan,&nbsp;Patricia P. Ogger,&nbsp;Ana Farias,&nbsp;Minerva Garcia Martín,&nbsp;Joy Nakawesi,&nbsp;Olivia Bedard,&nbsp;Candice Baker,&nbsp;Nadia Rosenthal,&nbsp;Cecilia Johansson","doi":"10.1002/eji.70043","DOIUrl":null,"url":null,"abstract":"<p>Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-<i>hACE2</i> transgene mice, a model previously shown to survive infection. 129xB6-K18-<i>hACE2</i> mice or littermate controls were infected with a low dose (5 × 10<sup>2</sup> PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, particularly CD8<sup>+</sup> effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 8","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70043","citationCount":"0","resultStr":"{\"title\":\"Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells\",\"authors\":\"Sophie Y. Guan,&nbsp;Patricia P. Ogger,&nbsp;Ana Farias,&nbsp;Minerva Garcia Martín,&nbsp;Joy Nakawesi,&nbsp;Olivia Bedard,&nbsp;Candice Baker,&nbsp;Nadia Rosenthal,&nbsp;Cecilia Johansson\",\"doi\":\"10.1002/eji.70043\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-<i>hACE2</i> transgene mice, a model previously shown to survive infection. 129xB6-K18-<i>hACE2</i> mice or littermate controls were infected with a low dose (5 × 10<sup>2</sup> PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, particularly CD8<sup>+</sup> effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.</p>\",\"PeriodicalId\":165,\"journal\":{\"name\":\"European Journal of Immunology\",\"volume\":\"55 8\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-08-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70043\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/eji.70043\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.70043","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

尽管病毒被清除,但许多SARS-CoV-2患者会出现慢性肺部症状和长期炎症。虽然这些临床表现与适应性免疫反应失调有关,但由于缺乏合适的动物模型,潜在的免疫病理学仍然知之甚少。为了研究SARS-CoV-2感染对肺部的长期影响,我们使用了129只小鼠和C57BL/6 (B6)-K18-hACE2转基因小鼠的遗传杂交,该模型先前被证明能够在感染中存活。129xB6-K18-hACE2小鼠或同窝对照感染低剂量(5 × 102 PFU)的祖先SARS-CoV-2。感染后第8天,病毒完全清除,体重完全恢复。然而,肺部和气道的长期炎症持续到感染后28天,并且与CD4+和CD8+ T细胞,特别是CD8+效应T细胞的存在有关。因此,该模型可能有助于进一步了解长期肺部炎症的驱动因素,以及测试针对SARS-CoV-2感染后长期肺部炎症的治疗策略和临床相关干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells

Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells

Many SARS-CoV-2 patients experience chronic pulmonary symptoms and long-term inflammation despite viral clearance. While these clinical manifestations have been linked to the dysregulation of the adaptive immune response, the underlying immunopathology remains poorly understood due to a lack of suitable animal models. To investigate long-term pulmonary consequences of SARS-CoV-2 infection, we used a genetic cross of 129 mice and C57BL/6 (B6)-K18-hACE2 transgene mice, a model previously shown to survive infection. 129xB6-K18-hACE2 mice or littermate controls were infected with a low dose (5 × 102 PFU) of ancestral SARS-CoV-2. Complete viral clearance and full recovery from weight loss occurred by day 8 post-infection. However, prolonged inflammation in the lung and airways persisted up to day 28 post-infection and was associated with the presence of CD4+ and CD8+ T cells, particularly CD8+ effector T cells. This model may therefore prove valuable for further understanding of drivers of long-term lung inflammation and for testing therapeutic strategies and clinically relevant interventions that can target long-term pulmonary inflammation following SARS-CoV-2 infection.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信