ArticleEBioMedicine2019
Transcriptome profiling reveals functional variation in Plasmodium falciparum parasites from controlled human malaria infection studies.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- Transmissibility of a new Plasmodium falciparum 3D7 bank for use in malaria volunteer infection studies evaluating transmission blocking interventions.Scientific reports · 2025Trial
- A novel computational pipeline foreLife · 2024Article
- Article
- Controlled Human Infection Models To Accelerate Vaccine Development.Clinical microbiology reviews · 2022Review
- Pervasive sequence-level variation in the transcriptome ofNAR genomics and bioinformatics · 2022Article
- Dramatic transcriptomic differences in Macaca mulatta and Macaca fascicularis with Plasmodium knowlesi infections.Scientific reports · 2021Article
- Article
- A comprehensive RNA handling and transcriptomics guide for high-throughput processing of Plasmodium blood-stage samples.Malaria journal · 2020Article
- Refining the transcriptome of the human malaria parasite Plasmodium falciparum using amplification-free RNA-seq.BMC genomics · 2020Article
- Human unconventional T cells in Plasmodium falciparum infection.Seminars in immunopathology · 2020Review
- Identification of a conserved var gene in different Plasmodium falciparum strains.Malaria journal · 2020Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe transcriptome of Plasmodium falciparum clinical isolates varies according to strain, mosquito bites, disease severity and clinical history. Therefore, it remains a challenge to directly interpret the parasite's transcriptomic information into a more general biological signature in a natural human malaria infection. These confounding variations can be potentially overcome with parasites derived from controlled-human malaria infection (CHMI) studies.
methodsWe performed CHMI studies in healthy and immunologically naïve volunteers receiving the same P. falciparum strain ((Sanaria® PfSPZ Challenge (NF54)), but with different sporozoite dosage and route of infection. Parasites isolated from these volunteers at the day of patency were subjected to in vitro culture for several generations and synchronized ring-stage parasites were subjected to transcriptome profiling.
findingsWe observed clear deviations between CHMI-derived parasites from volunteer groups receiving different PfSPZ dose and route. CHMI-derived parasites and the pre-mosquito strain used for PfSPZ generation showed significant transcriptional variability for gene clusters associated with malaria pathogenesis, immune evasion and transmission. These transcriptional variation signature clusters were also observed in the transcriptome of P. falciparum isolates from acute clinical infections.
interpretationOur work identifies a previously unrecognized transcriptional pattern in malaria infections in a non-immune background. Significant transcriptome heterogeneity exits between parasites derived from human infections and the pre-mosquito strain, implying that the malaria parasites undergo a change in functional state to adapt to its host environment. Our work also highlights the potential use of transcriptomics data from CHMI study advance our understanding of malaria parasite adaptation and transmission in humans. FUND: This work is supported by German Israeli Foundation, German ministry for education and research, MOE Tier 1 from the Singapore Ministry of Education Academic Research Fund, Singapore Ministry of Health's National Medical Research Council, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA and the German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung-DZIF).
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