ArticlePLoS pathogens2021
Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322581 (A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali), which is not on this map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali
Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- The case for exploring innate memory in Plasmodium infection.Current opinion in microbiology · 2026Review
- The endemic dilemma: why whole sporozoite malaria vaccine efficacy falls in the field.Trends in parasitology · 2026Review
- A narrative review of heterogeneity in SARS-CoV-2 infection outcomes and vaccine efficacy: strategizing pandemic preparedness in Africa.Frontiers in public health · 2026Review
- Hidden hematological, biochemical and immune costs of asymptomatic malaria infections in semi-wild chimpanzees.bioRxiv : the preprint server for biology · 2025Article
- Age is an intrinsic driver of inflammatory responses to malaria.Nature communications · 2025Article
- Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection.Nature communications · 2025Article
- Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025Review
- Generalist Malaria Parasites and Host Imprinting: Unveiling Transcriptional Memory.Molecular biology and evolution · 2025Article
- Article
- A Novel Inhibitor against the Bromodomain Protein 1 of the Malaria Pathogen Plasmodium Falciparum.ChemMedChem · 2025Article
- Single-cell transcriptomics reveals inter-ethnic variation in immune response to Falciparum malaria.American journal of human genetics · 2025Article
- Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages.Frontiers in immunology · 2025Article
- The type 2 immune response in gut homeostasis and parasite transmission in malaria.Trends in parasitology · 2025Review
- Lupus and other autoimmune diseases: Epidemiology in the population of African ancestry and diagnostic and management challenges in Africa.The journal of allergy and clinical immunology. Global · 2024Review
- The impact of Plasmodium-driven immunoregulatory networks on immunity to malaria.Nature reviews. Immunology · 2024Review
- Cellular immune response to SARS-CoV-2 and clinical presentation in individuals exposed to endemic malaria.Cell reports · 2024Article
- Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells.PNAS nexus · 2024Article
- Transcriptomic analyses of differentially expressed human genes, micro RNAs and long-non-coding RNAs in severe, symptomatic and asymptomatic malaria infection.Scientific reports · 2024Article
- Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms.Nature communications · 2024Article
- Immunological factors linked to geographical variation in vaccine responses.Nature reviews. Immunology · 2024Review
Corrections and comments
- Update of
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
In malaria-naïve children and adults, Plasmodium falciparum-infected red blood cells (Pf-iRBCs) trigger fever and other symptoms of systemic inflammation. However, in endemic areas where individuals experience repeated Pf infections over many years, the risk of Pf-iRBC-triggered inflammatory symptoms decreases with cumulative Pf exposure. The molecular mechanisms underlying these clinical observations remain unclear. Age-stratified analyses of uninfected, asymptomatic Malian individuals before the malaria season revealed that monocytes of adults produced lower levels of inflammatory cytokines (IL-1β, IL-6 and TNF) in response to Pf-iRBC stimulation compared to monocytes of Malian children and malaria-naïve U.S. adults. Moreover, monocytes of Malian children produced lower levels of IL-1β and IL-6 following Pf-iRBC stimulation compared to 4-6-month-old infants. Accordingly, monocytes of Malian adults produced more IL-10 and expressed higher levels of the regulatory molecules CD163, CD206, Arginase-1 and TGM2. These observations were recapitulated in an in vitro system of monocyte to macrophage differentiation wherein macrophages re-exposed to Pf-iRBCs exhibited attenuated inflammatory cytokine responses and a corresponding decrease in the epigenetic marker of active gene transcription, H3K4me3, at inflammatory cytokine gene loci. Together these data indicate that Pf induces epigenetic reprogramming of monocytes/macrophages toward a regulatory phenotype that attenuates inflammatory responses during subsequent Pf exposure. Trial Registration: ClinicalTrials.gov NCT01322581.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.