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

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 () and Jigang Wang ()
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Jiayun Chen: China Academy of Chinese Medical Sciences
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
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
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
Jigang Wang: China Academy of Chinese Medical Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-52223-7

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