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

• Published in: Nature communications Vol. 16; no. 1; pp. 1540 - 21
• Main Authors: Chen, Jiayun, Bai, Yunmeng, He, Xueling, Xiao, Wei, Chen, Lina, Wong, Yin Kwan, Wang, Chen, Gao, Peng, Cheng, Guangqing, Xu, Liting, Yang, Chuanbin, Liao, Fulong, Han, Guang, Sun, Jichao, Xu, Chengchao, Wang, Jigang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.02.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 45/91; 49; 49/105; 631/114/2401; 631/61/212/2019; 64/60; 692/699/255/1715; Animals; Antigen presentation; Antigens; Antimalarial agents; Antimalarials - pharmacology; Antimalarials - therapeutic use; Artemisinin; Artemisinins - pharmacology; Artemisinins - therapeutic use; Artesunate; Artesunate - pharmacology; Artesunate - therapeutic use; Blood parasites; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain - drug effects; Brain - metabolism; Brain - parasitology; Brain - pathology; CD8 antigen; Complications; Cytotoxicity; Disease Models, Animal; Disease Progression; Encephalopathy; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Extracellular matrix; Gene Expression Profiling; Host-Parasite Interactions; Humanities and Social Sciences; Inflammation; Injury analysis; Interferon-gamma - metabolism; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Malaria; Malaria, Cerebral - drug therapy; Malaria, Cerebral - genetics; Malaria, Cerebral - immunology; Malaria, Cerebral - parasitology; Malaria, Cerebral - pathology; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; multidisciplinary; Parasites; Science; Science (multidisciplinary); Spatial analysis; Transcriptome; Transcriptomes; Transcriptomics; Vector-borne diseases; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52223-7

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.