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A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses

Article scientifique 2025 Anglais

Résumé

Factors governing the clinical trajectory of Plasmodium falciparum infection remain an important area of investigation. Here we present transcriptomic, proteomic and metabolomic analyses comparing clinical subtypes of severe Plasmodium falciparum malaria to matched controls with uncomplicated disease in 79 children from Mali. MMP8, IL1R2, and ARG1 transcription is higher across cerebral malaria, severe malarial anemia, and concurrent cerebral malaria and severe malarial anemia, indicating a shared inflammatory signature. Tissue inhibitor of metalloproteinases 1 is the most upregulated protein in cerebral malaria, which along with elevated MMP8 and MMP9 transcription, underscores the importance of the metalloproteinase pathway in central nervous system pathophysiology. L-arginine metabolites are decreased in cerebral malaria, which coupled with increased ARG1 transcription suggests a putative mechanism impairing cerebral vasodilation. Using multi-omics approaches, we thus describe the inflammatory cascade in severe malaria syndromes, and identify potential therapeutic targets and biological markers.

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Sobota, R., Stucke, E., Coulibaly, D., Lawton, J., Cummings, B., Sebastian, S., Dara, A., Munro, J., Ouattara, A., Koné, A., Kané, B., Traoré, K., Guindo, B., Tangara, B., Niangaly, A., Ventimiglia, N., Daou, M., Diarra, I., Tolo, Y., Sissoko, M., Maïga, F., Diawara, A., Traore, A., Thera, A., Laurens, M., Lyke, K., Kouriba, B., Doumbo, O., Plowe, C., Goodlett, D., Silva, J., Théra, M., Travassos, M. (2025). A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses. https://doi.org/10.1038/s41467-025-59281-5

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Auteur(s)

Rafal S. Sobota Emily M. Stucke Drissa Coulibaly Jonathan G. Lawton Bryan E. Cummings Savy Sebastian Antoine Dara James B. Munro Amed Ouattara Abdoulaye K. Koné Bourama Kané Karim Traoré Bouréima Guindo Bourama Tangara Amadou Niangaly Noah T. Ventimiglia Modibo Daou Issa Diarra Youssouf Tolo Mody Sissoko Fayçal Maïga A. Diawara Amidou Traore Ali Thera Matthew B. Laurens Kirsten E. Lyke Bourèma Kouriba Ogobara K. Doumbo Christopher V. Plowe David R. Goodlett Joana C. Silva Mahamadou A. Théra Mark A. Travassos

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