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

May 19, 2025

Experts: 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

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.
© 2025. The Author(s).

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ABOUT THE EXPERTS

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

Rafal S Sobota

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, IL, USA.

Emily M Stucke

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Drissa Coulibaly

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Jonathan G Lawton

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Bryan E Cummings

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Savy Sebastian

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Antoine Dara

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

James B Munro

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

Amed Ouattara

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Abdoulaye K Kone

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Bourama Kane

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Karim Traoré

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Bouréima Guindo

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Bourama M Tangara

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Amadou Niangaly

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Noah T Ventimiglia

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Modibo Daou

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Issa Diarra

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Youssouf Tolo

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Mody Sissoko

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Fayçal Maiga

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Aichatou Diawara

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Amidou Traore

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Ali Thera

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Matthew B Laurens

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Kirsten E Lyke

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Bourema Kouriba

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Ogobara K Doumbo

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Christopher V Plowe

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

David R Goodlett

Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

Joana C Silva

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

Mahamadou A Thera

Malaria Research and Training Center, University of Sciences Techniques and Technologies, Bamako, Mali.

Mark A Travassos

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA. mtravass@som.umaryland.edu.