Single-cell profiling reveals immunoregulation of artemisinin on CD8+GZMB+ T cells via JAK2-STAT3 in malaria-infected mice
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.
Authors
- Wei Zhou (ORCID: https://orcid.org/0000-0001-9636-7963)
- Yin‐Kwan Wong (ORCID: https://orcid.org/0000-0003-2813-488X)
- Youyou Tu (ORCID: https://orcid.org/0000-0001-9781-3857)
- Yiqiang Wu
- Juanjuan Ou (ORCID: https://orcid.org/0000-0003-1665-4300)
- Fulong Liao
- Jianyou Wang
- Xueling He
- Yanwei Hu (ORCID: https://orcid.org/0000-0001-9891-5310)
- Guangqing Cheng
- Yunmeng Bai (ORCID: https://orcid.org/0000-0001-7915-4501)
- Chengchao Xu (ORCID: https://orcid.org/0000-0003-4558-7581)
- Chen Wang
- Xiaohong Liu (ORCID: https://orcid.org/0000-0003-4795-3039)
- Weidong Zhang (ORCID: https://orcid.org/0000-0002-7384-2490)
- Lina Chen (ORCID: https://orcid.org/0000-0001-6699-6603)
- Jigang Wang (ORCID: https://orcid.org/0000-0002-0575-0105)
- Yanxia Liu (ORCID: https://orcid.org/0000-0001-7311-0006)
- Yue Gao (ORCID: https://orcid.org/0000-0002-9217-5021)
- Jiayun Chen (ORCID: https://orcid.org/0000-0002-1622-0783)
- Xing Zhang (ORCID: https://orcid.org/0000-0003-1643-6362)
Institutions
- Central South University of Forestry and Technology (CN)
- Central South University (CN)
- Chongqing University (CN)
- National University of Singapore (SG)
- Capital Medical University (CN)
- Guangdong Pharmaceutical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Beijing Chao-Yang Hospital, Capital Medical University (CN)
- Southern University of Science and Technology (CN)
- Sichuan Cancer Hospital (CN)
- Chongqing Institute of Green and Intelligent Technology (CN)
- Xinjiang University (CN)
Publication Details
- Journal
- The Innovation
- Published
- 2025-08-15
- DOI
- https://doi.org/10.1016/j.xinn.2025.101080
- Citations
- 1
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 1.88