Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria
Issued Date
2025-01-01
Resource Type
eISSN
17444292
Scopus ID
2-s2.0-105013626127
Journal Title
Molecular Systems Biology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Systems Biology (2025)
Suggested Citation
Studniberg S.I., Bafit M., Ioannidis L.J., Worley M.J., Trianty L., Utami R.A.S., Puspitasari A.M., Apriyanti D., Coutrier F.N., Poespoprodjo J.R., Kenangalem E., Andries B., Prayoga P., Price R.N., Noviyanti R., Garnham A.L., Hansen D.S. Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria. Molecular Systems Biology (2025). doi:10.1038/s44320-025-00135-z Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111843
Title
Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria
Author's Affiliation
University of Melbourne
Monash University
Universitas Gadjah Mada
Nuffield Department of Medicine
Walter and Eliza Hall Institute of Medical Research
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
Exeins Health Initiative
Mimika District Hospital
Papuan Health and Community Development Foundation
Eijkman Research Centre for Molecular Biology
Monash University
Universitas Gadjah Mada
Nuffield Department of Medicine
Walter and Eliza Hall Institute of Medical Research
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
Exeins Health Initiative
Mimika District Hospital
Papuan Health and Community Development Foundation
Eijkman Research Centre for Molecular Biology
Corresponding Author(s)
Other Contributor(s)
Abstract
Although asymptomatic malaria was historically perceived as innocuous, emerging evidence revealed an immunosuppressive signature induced by asymptomatic Plasmodium falciparum infections. To examine if a similar process occurs in Plasmodium vivax malaria, we pursued a systems approach, integrating transcriptional profiling together with previously reported and novel mass cytometry phenotypes from individuals with symptomatic and asymptomatic P. vivax malaria. Symptomatic P. vivax malaria featured upregulation of anti-inflammatory pathways and checkpoint receptors. A profound downregulation of transcripts with roles in monocyte function was observed in symptomatic P. vivax malaria. This reduction in monocyte transcriptional activity was accompanied by a significant depletion of CCR2<sup>+</sup>CXCR4<sup>+</sup> classical monocytes in symptomatic individuals. Despite allowing transcriptional profiles supporting T-cell differentiation, dysregulation of genes associated with monocyte activation and the inflammasome was also evident in individuals carrying P. vivax asymptomatic infections. Our results identify monocyte dysregulation as a key feature of the response to P. vivax malaria and support the concept that asymptomatic infection is not innocuous and might not support all immune processes required to eliminate parasitemia or efficiently respond to vaccination.