A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses
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.
Authors
- Joana C. Silva (ORCID: https://orcid.org/0000-0001-6502-7026)
- Ali Thera
- Rafal S. Sobota (ORCID: https://orcid.org/0000-0002-5945-5830)
- Bourèma Kouriba (ORCID: https://orcid.org/0000-0002-3419-5972)
- Matthew B. Laurens (ORCID: https://orcid.org/0000-0003-3874-581X)
- Beryl B. Cummings (ORCID: https://orcid.org/0000-0001-6346-1646)
- Emily M. Stucke (ORCID: https://orcid.org/0000-0002-8256-3290)
- David R. Goodlett (ORCID: https://orcid.org/0000-0002-8045-8200)
- Mark A. Travassos (ORCID: https://orcid.org/0000-0002-6045-3322)
- Christopher V. Plowe (ORCID: https://orcid.org/0000-0002-0045-9888)
- Issa Diarra
- Drissa Coulibaly (ORCID: https://orcid.org/0000-0002-7412-0940)
- James B. Munro (ORCID: https://orcid.org/0000-0003-3067-6434)
- Noah T. Ventimiglia
- Bourama Tangara
- Antoine Dara (ORCID: https://orcid.org/0000-0002-7739-4437)
- Jonathan G. Lawton
- Bourama Kané
- Kirsten E. Lyke (ORCID: https://orcid.org/0000-0002-4966-0830)
- Youssouf Tolo
- Amadou Niangaly (ORCID: https://orcid.org/0000-0003-3768-8446)
- Mahamadou A. Théra (ORCID: https://orcid.org/0000-0002-2679-035X)
- Abdoulaye K. Koné (ORCID: https://orcid.org/0000-0003-4101-5391)
- Karim Traoré (ORCID: https://orcid.org/0000-0002-9553-6611)
- Fayçal Maïga
- Sunit Sebastian
- Mody Sissoko
- Amed Ouattara (ORCID: https://orcid.org/0000-0003-1964-7130)
- Modibo Daou
- Bouréima Guindo
- A. Diawara
- Ogobara K. Doumbo
- Amidou Traore
Institutions
- Northwestern University (US)
- University of Maryland, Baltimore (US)
- University of Victoria (CA)
- University of Bamako (ML)
- Université des Sciences, des Techniques et des Technologies de Bamako (ML)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-18
- DOI
- https://doi.org/10.1038/s41467-025-59281-5
- Citations
- 5
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 9.39
Funders
- Howard Hughes Medical Institute
- Burroughs Wellcome Fund
- National Institutes of Health
- School of Medicine, University of Maryland
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke
- National Center for Advancing Translational Sciences