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

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. Kone, Bourama Kane, Karim Traoré, Bouréima Guindo, Bourama M. Tangara, Amadou Niangaly, Noah T. Ventimiglia, Modibo Daou, Issa Diarra, Youssouf Tolo, Mody Sissoko, Fayçal Maiga, Aichatou Diawara, Amidou Traore, Ali Thera, Matthew B. Laurens, Kirsten E. Lyke, Bourema Kouriba, Ogobara K. Doumbo, Christopher V. Plowe, David R. Goodlett, Joana C. Silva, Mahamadou A. Thera and Mark A. Travassos ()
Additional contact information
Rafal S. Sobota: University of Maryland School of Medicine
Emily M. Stucke: University of Maryland School of Medicine
Drissa Coulibaly: University of Sciences Techniques and Technologies
Jonathan G. Lawton: University of Maryland School of Medicine
Bryan E. Cummings: University of Maryland School of Medicine
Savy Sebastian: University of Maryland School of Medicine
Antoine Dara: University of Sciences Techniques and Technologies
James B. Munro: University of Maryland School of Medicine
Amed Ouattara: University of Maryland School of Medicine
Abdoulaye K. Kone: University of Sciences Techniques and Technologies
Bourama Kane: University of Sciences Techniques and Technologies
Karim Traoré: University of Sciences Techniques and Technologies
Bouréima Guindo: University of Sciences Techniques and Technologies
Bourama M. Tangara: University of Sciences Techniques and Technologies
Amadou Niangaly: University of Sciences Techniques and Technologies
Noah T. Ventimiglia: University of Maryland School of Medicine
Modibo Daou: University of Sciences Techniques and Technologies
Issa Diarra: University of Sciences Techniques and Technologies
Youssouf Tolo: University of Sciences Techniques and Technologies
Mody Sissoko: University of Sciences Techniques and Technologies
Fayçal Maiga: University of Sciences Techniques and Technologies
Aichatou Diawara: University of Sciences Techniques and Technologies
Amidou Traore: University of Sciences Techniques and Technologies
Ali Thera: University of Sciences Techniques and Technologies
Matthew B. Laurens: University of Maryland School of Medicine
Kirsten E. Lyke: University of Maryland School of Medicine
Bourema Kouriba: University of Sciences Techniques and Technologies
Ogobara K. Doumbo: University of Sciences Techniques and Technologies
Christopher V. Plowe: University of Maryland School of Medicine
David R. Goodlett: University of Victoria
Joana C. Silva: University of Maryland School of Medicine
Mahamadou A. Thera: University of Sciences Techniques and Technologies
Mark A. Travassos: University of Maryland School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-59281-5

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