Nature Communications (May 2025)
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,
- Mark A. Travassos
Affiliations
- Rafal S. Sobota
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Emily M. Stucke
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Drissa Coulibaly
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Jonathan G. Lawton
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Bryan E. Cummings
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Savy Sebastian
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Antoine Dara
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- James B. Munro
- Institute for Genome Sciences, University of Maryland School of Medicine
- Amed Ouattara
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Abdoulaye K. Kone
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Bourama Kane
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Karim Traoré
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Bouréima Guindo
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Bourama M. Tangara
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Amadou Niangaly
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Noah T. Ventimiglia
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Modibo Daou
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Issa Diarra
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Youssouf Tolo
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Mody Sissoko
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Fayçal Maiga
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Aichatou Diawara
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Amidou Traore
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Ali Thera
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Matthew B. Laurens
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Kirsten E. Lyke
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Bourema Kouriba
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Ogobara K. Doumbo
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Christopher V. Plowe
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- David R. Goodlett
- Department of Biochemistry and Microbiology, University of Victoria
- Joana C. Silva
- Institute for Genome Sciences, University of Maryland School of Medicine
- Mahamadou A. Thera
- Malaria Research and Training Center, University of Sciences Techniques and Technologies
- Mark A. Travassos
- Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- DOI
- https://doi.org/10.1038/s41467-025-59281-5
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 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.
