Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria
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.
Authors
- Benediktus Andries (ORCID: https://orcid.org/0000-0002-0354-456X)
- Farah N. Coutrier (ORCID: https://orcid.org/0000-0003-3141-0697)
- Ric N. Price (ORCID: https://orcid.org/0000-0003-2000-2874)
- Lisa J. Ioannidis (ORCID: https://orcid.org/0000-0003-1287-7347)
- Alexandra L. Garnham (ORCID: https://orcid.org/0000-0002-8312-8450)
- Retno A. S. Utami (ORCID: https://orcid.org/0000-0001-6142-0496)
- Rintis Noviyanti (ORCID: https://orcid.org/0000-0003-1383-3274)
- Leily Trianty (ORCID: https://orcid.org/0000-0002-4368-476X)
- Agatha Mia Puspitasari (ORCID: https://orcid.org/0000-0003-4191-5023)
- Diana S. Hansen (ORCID: https://orcid.org/0000-0003-4511-7918)
- Enny Kenangalem (ORCID: https://orcid.org/0000-0002-0481-7435)
- Jeanne Rini Poespoprodjo (ORCID: https://orcid.org/0000-0003-1573-734X)
- Stephanie I. Studniberg (ORCID: https://orcid.org/0000-0002-9452-4977)
- Dwi Apriyanti (ORCID: https://orcid.org/0000-0003-1042-9583)
- Mariam Bafit
- Matthew J. Worley
- Pak Prayoga
Institutions
- Universitas Gadjah Mada (ID)
- The University of Melbourne (AU)
- State University of Papua (ID)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Mahidol University (TH)
- Discovery Institute (US)
- Angkor Hospital for Children (KH)
- Community Foundation (US)
- Eijkman Institute for Molecular Biology (ID)
- Australian Regenerative Medicine Institute (AU)
- Nuffield Orthopaedic Centre (GB)
- Charles Darwin University (AU)
- Jakarta Theological Seminary (ID)
- University of Oxford (GB)
- Menzies School of Health Research (AU)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- Monash University (AU)
Publication Details
- Journal
- Molecular Systems Biology
- Published
- 2025-08-19
- DOI
- https://doi.org/10.1038/s44320-025-00135-z
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- LifeArc
- Australian Academy of Science
- National Health and Medical Research Council