Single-cell profiling reveals immunoregulation of artemisinin on CD8+GZMB+ T cells via JAK2-STAT3 in malaria-infected mice.

IF 25.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
The Innovation Pub Date : 2025-08-14 eCollection Date: 2025-09-08 DOI:10.1016/j.xinn.2025.101080
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
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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.

单细胞分析揭示了青蒿素通过JAK2-STAT3对疟疾感染小鼠CD8+GZMB+ T细胞的免疫调节。
疟疾是一种普遍和破坏性疾病,其特点是全身性并发症和宿主对疟原虫感染的免疫反应失调。青蒿素衍生物,特别是青蒿琥酯(ART),是疟疾治疗战略的基石。虽然确切的免疫调节机制尚不清楚,但抗逆转录病毒治疗不仅能杀死寄生虫,还能影响宿主的免疫稳态。在这项研究中,我们使用单细胞RNA测序来表征来自多种小鼠组织(包括肝脏、脾脏和外周血)的241,837个细胞在伯氏疟原虫ANKA (PbA)感染和抗逆转录病毒治疗后的细胞景观。同时,我们在不同的免疫细胞类型中观察到显著的转录组变化,肝脏在对PbA感染的反应中表现出最显著的变化。值得注意的是,以细胞因子和细胞毒模块评分升高为特征的CD8+GZMB+ T淋巴细胞在驱动肝损伤中起关键作用。此外,ART通过JAK2-STAT3途径调节这种致病亚型,降低其频率并减轻其炎症反应。我们的研究为探索疟疾免疫发病机制提供了宝贵的数据资源,并阐明了抗逆转录病毒药物在感染宿主体内的一种新的免疫调节机制。
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来源期刊
The Innovation
The Innovation MULTIDISCIPLINARY SCIENCES-
CiteScore
38.30
自引率
1.20%
发文量
134
审稿时长
6 weeks
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.
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