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, Jigang Wang
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. By integrating single-cell and spatial transcriptomic analysis, Chen et al. profile the cellular disruptions in the murine brain during cerebral malaria and after artemisinin treatment.