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The spatiotemporal transcriptional profiling of murine brain during cerebral malaria progression and after artemisinin treatment

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  • Jiayun Chen

    (China Academy of Chinese Medical Sciences
    Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
    Guangdong Pharmaceutical University)

  • Yunmeng Bai

    (Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology))

  • Xueling He

    (China Academy of Chinese Medical Sciences)

  • Wei Xiao

    (Guangdong Pharmaceutical University
    Southern Medical University)

  • Lina Chen

    (China Academy of Chinese Medical Sciences)

  • Yin Kwan Wong

    (Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology))

  • Chen Wang

    (China Academy of Chinese Medical Sciences)

  • Peng Gao

    (China Academy of Chinese Medical Sciences
    Henan University)

  • Guangqing Cheng

    (China Academy of Chinese Medical Sciences)

  • Liting Xu

    (China Academy of Chinese Medical Sciences)

  • Chuanbin Yang

    (Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology))

  • Fulong Liao

    (China Academy of Chinese Medical Sciences)

  • Guang Han

    (Henan University)

  • Jichao Sun

    (Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology))

  • Chengchao Xu

    (China Academy of Chinese Medical Sciences
    Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology))

  • Jigang Wang

    (China Academy of Chinese Medical Sciences
    Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
    Guangdong Pharmaceutical University
    Southern Medical University)

Abstract

Cerebral malaria (CM) is a severe encephalopathy caused by Plasmodium parasite infection, resulting in thousands of annual deaths and neuro-cognitive sequelae even after anti-malarial drugs treatment. Despite efforts to dissect the mechanism, the cellular transcriptomic reprogramming within the spatial context remains elusive. Here, we constructed single-cell and spatial transcriptome atlases of experimental CM (ECM) male murine brain tissues with or without artesunate (ART) treatment. We identified activated inflammatory endothelial cells during ECM, characterized by a disrupted blood-brain barrier, increased antigen presentation, and leukocyte adhesion. We also observed that inflammatory microglia enhance antigen presentation pathway such as MHC-I to CD8+ cytotoxic T cells. The latter underwent an inflammatory state transition with up-regulated cytokine expression and cytotoxic activity. Multi-omics analysis revealed that the activated interferon-gamma response of injured neurons during ECM and persisted after ART treatment. Overall, our research provides valuable resources for understanding malaria parasite-host interaction mechanisms and adjuvant therapy development.

Suggested Citation

  • Jiayun Chen & Yunmeng Bai & Xueling He & Wei Xiao & Lina Chen & Yin Kwan Wong & Chen Wang & Peng Gao & Guangqing Cheng & Liting Xu & Chuanbin Yang & Fulong Liao & Guang Han & Jichao Sun & Chengchao Xu, 2025. "The spatiotemporal transcriptional profiling of murine brain during cerebral malaria progression and after artemisinin treatment," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-52223-7
    DOI: 10.1038/s41467-024-52223-7
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