A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses
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 uncomplicat...
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2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59281-5 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rafal S. Sobota |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-724ff740a22a48559f133c6aef7eb65b |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-724ff740a22a48559f133c6aef7eb65b2025-08-20T01:51:36ZengNature PortfolioNature Communications2041-17232025-05-0116111410.1038/s41467-025-59281-5A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analysesRafal S. Sobota0Emily M. Stucke1Drissa Coulibaly2Jonathan G. Lawton3Bryan E. Cummings4Savy Sebastian5Antoine Dara6James B. Munro7Amed Ouattara8Abdoulaye K. Kone9Bourama Kane10Karim Traoré11Bouréima Guindo12Bourama M. Tangara13Amadou Niangaly14Noah T. Ventimiglia15Modibo Daou16Issa Diarra17Youssouf Tolo18Mody Sissoko19Fayçal Maiga20Aichatou Diawara21Amidou Traore22Ali Thera23Matthew B. Laurens24Kirsten E. Lyke25Bourema Kouriba26Ogobara K. Doumbo27Christopher V. Plowe28David R. Goodlett29Joana C. Silva30Mahamadou A. Thera31Mark A. Travassos32Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research and Training Center, University of Sciences Techniques and TechnologiesInstitute for Genome Sciences, University of Maryland School of MedicineMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineDepartment of Biochemistry and Microbiology, University of VictoriaInstitute for Genome Sciences, University of Maryland School of MedicineMalaria Research and Training Center, University of Sciences Techniques and TechnologiesMalaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-59281-5 |
| spellingShingle | 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 A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses Nature Communications |
| title | A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses |
| title_full | A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses |
| title_fullStr | A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses |
| title_full_unstemmed | A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses |
| title_short | A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses |
| title_sort | shared inflammatory signature across severe malaria syndromes manifested by transcriptomic proteomic and metabolomic analyses |
| url | https://doi.org/10.1038/s41467-025-59281-5 |
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