A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses
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.
Article Details
Authors (33)
Rafal S. Sobota
Emily M. Stucke
Drissa Coulibaly
Jonathan G. Lawton
Bryan E. Cummings
Savy Sebastian
Antoine Dara
James B. Munro
Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School
Amed Ouattara
Abdoulaye K. Kone
Bourama Kane
Karim Traore
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
Bourèma Kouriba
Ogobara K. Doumbo
Christopher V. Plowe
David R. Goodlett
Joana C. Silva
Mahamadou A. Thera
Mark A. Travassos