{"title":"Single-cell profiling reveals immunoregulation of artemisinin on CD8<sup>+</sup>GZMB<sup>+</sup> T cells via JAK2-STAT3 in malaria-infected mice.","authors":"Jiayun Chen, Peng Gao, Xueling He, Yanwei Hu, Wei Zhou, Yanxia Liu, Jianyou Wang, Xiaohong Liu, Yunmeng Bai, Lina Chen, Chen Wang, Guangqing Cheng, Xing Zhang, Yin Kwan Wong, Fulong Liao, Chengchao Xu, Juanjuan Ou, Yiqiang Wu, Wei Zhang, Yue Gao, Youyou Tu, Jigang Wang","doi":"10.1016/j.xinn.2025.101080","DOIUrl":null,"url":null,"abstract":"<p><p>Malaria, a pervasive and devastating disease, is characterized by systemic complications and dysregulated host immune responses to <i>Plasmodium</i> infection. Artemisinin derivatives, particularly artesunate (ART), are a cornerstone in malaria treatment strategies. Although the precise immunomodulatory mechanisms remain unclear, ART not only kills parasites but also impacts host immune homeostasis. In this study, we employed single-cell RNA sequencing to characterize the cellular landscape of 241,837 cells from multiple murine tissues (including liver, spleen, and peripheral blood) upon <i>Plasmodium berghei ANKA</i> (PbA) infection and after ART treatment. Meanwhile, we observed significant transcriptomic shifts across diverse immune cell types, with the liver exhibiting the most pronounced changes in response to PbA infection. Notably, CD8<sup>+</sup>GZMB<sup>+</sup> T lymphocytes, characterized by elevated cytokine and cytotoxic module scores, play a pivotal role in driving hepatic injury. Furthermore, ART modulated this pathogenic subtype via the JAK2-STAT3 pathway, reducing its frequency and mitigating its inflammatory response. Our research provides a valuable dataset resource for exploring malaria immunopathogenesis and elucidates a novel immunoregulatory mechanism of ART within the infected host.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"6 9","pages":"101080"},"PeriodicalIF":25.7000,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447648/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Innovation","FirstCategoryId":"95","ListUrlMain":"https://doi.org/10.1016/j.xinn.2025.101080","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/8 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Malaria, a pervasive and devastating disease, is characterized by systemic complications and dysregulated host immune responses to Plasmodium infection. Artemisinin derivatives, particularly artesunate (ART), are a cornerstone in malaria treatment strategies. Although the precise immunomodulatory mechanisms remain unclear, ART not only kills parasites but also impacts host immune homeostasis. In this study, we employed single-cell RNA sequencing to characterize the cellular landscape of 241,837 cells from multiple murine tissues (including liver, spleen, and peripheral blood) upon Plasmodium berghei ANKA (PbA) infection and after ART treatment. Meanwhile, we observed significant transcriptomic shifts across diverse immune cell types, with the liver exhibiting the most pronounced changes in response to PbA infection. Notably, CD8+GZMB+ T lymphocytes, characterized by elevated cytokine and cytotoxic module scores, play a pivotal role in driving hepatic injury. Furthermore, ART modulated this pathogenic subtype via the JAK2-STAT3 pathway, reducing its frequency and mitigating its inflammatory response. Our research provides a valuable dataset resource for exploring malaria immunopathogenesis and elucidates a novel immunoregulatory mechanism of ART within the infected host.
期刊介绍:
The Innovation is an interdisciplinary journal that aims to promote scientific application. It publishes cutting-edge research and high-quality reviews in various scientific disciplines, including physics, chemistry, materials, nanotechnology, biology, translational medicine, geoscience, and engineering. The journal adheres to the peer review and publishing standards of Cell Press journals.
The Innovation is committed to serving scientists and the public. It aims to publish significant advances promptly and provides a transparent exchange platform. The journal also strives to efficiently promote the translation from scientific discovery to technological achievements and rapidly disseminate scientific findings worldwide.
Indexed in the following databases, The Innovation has visibility in Scopus, Directory of Open Access Journals (DOAJ), Web of Science, Emerging Sources Citation Index (ESCI), PubMed Central, Compendex (previously Ei index), INSPEC, and CABI A&I.