Evidence map›Paper›PMID 39161730›Full record

ArticlePNAS nexus2024

Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells.

Jason Nideffer, Maureen Ty, Michele Donato, Rek John, Richard Kajubi, Xuhuai Ji, Felistas Nankya, Kenneth Musinguzi, Kathleen Dantzler Press, Nora Yang and 9 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PNAS nexus, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04978272 (Enhancing Immunity to Malaria in Young Children With Effective Chemoprevention), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

NCT04978272 phase3active not recruitingnot on this map

Enhancing Immunity to Malaria in Young Children With Effective Chemoprevention

TypeinterventionalSponsorGrant Dorsey, M.D, Ph.D.Ran2022 to 2027Enrolled924ConditionsMalariaArmsDihydroartemisinin-piperaquine (DP), DP Placebo
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025
    Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Jason NidefferDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-4421-8656
Maureen TyDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.
Michele DonatoDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.
Rek JohnInfectious Diseases Research Collaboration, Kampala, Uganda.ORCID https://orcid.org/0000-0003-4063-0763
Richard KajubiInfectious Diseases Research Collaboration, Kampala, Uganda.ORCID https://orcid.org/0000-0002-9179-9182
Xuhuai JiInstitute for Immunity, Infection, and Transplantation, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-1768-6403
Felistas NankyaInfectious Diseases Research Collaboration, Kampala, Uganda.
Kenneth MusinguziInfectious Diseases Research Collaboration, Kampala, Uganda.ORCID https://orcid.org/0000-0001-6890-8988
Kathleen Dantzler PressDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-6548-7513
Nora YangDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0009-0008-6839-898X
Kylie CamanagDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0009-0000-8858-4378
Bryan GreenhouseDepartment of Medicine, University of California, San Francisco, CA 94142, USA.
Moses KamyaSchool of Medicine, Makerere University, Kampala, Uganda.ORCID https://orcid.org/0000-0001-9106-4234
Margaret E FeeneyDepartment of Pediatrics, University of California, San Francisco, CA 94142, USA.ORCID https://orcid.org/0000-0002-2515-2989
Grant DorseyDepartment of Medicine, University of California, San Francisco, CA 94142, USA.ORCID https://orcid.org/0000-0003-0740-0317
Paul J UtzDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.
Bali PulendranDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.
Purvesh KhatriDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-4143-4708
Prasanna JagannathanDepartment of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0001-6305-758X

Funding

Transmission ProjectU19AI089674 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW G DORSEY, MOSES Robert KAMYA · 2010 to 2026
$29.3M
Systems biological assessment of T cell responses to vaccinationU19AI167903 · NIAID · STANFORD UNIVERSITY · PI BALI PULENDRAN · 2022 to 2026
$13.2M
The role of γδ T cells in fetal and infant immune defense against malariaR01AI093615 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FEENEY, MARGARET E · 2011 to 2025
$9.1M
Computational models of naturally acquired immunity to falciparum malariaU01AI150741 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUTTE, ATUL J, GREENHOUSE, BRYAN R · 2020 to 2024
$7.4M
EMERGING INFECTIOUS DISEASEST32AI007502 · NIAID · STANFORD UNIVERSITY · PI Prasanna Jagannathan, DAVID A. RELMAN · 1995 to 2026
$6.8M
Enhancing immunity to malaria in young children with effective chemopreventionU01AI155325 · NIAID · STANFORD UNIVERSITY · PI JAGANNATHAN, PRASANNA · 2021 to 2025
$6.3M
Systems biological assessment of vaccination-induced protective immunity in African childrenU01AI165527 · NIAID · STANFORD UNIVERSITY · PI James Beeson, BALI PULENDRAN · 2022 to 2026
$4.0M
Stanford ChEM-H Chemistry/Biology Interface Predoctoral Training ProgramT32GM139791 · NIGMS · STANFORD UNIVERSITY · PI Carolyn Bertozzi, Christine Jacobs-Wagner · 2021 to 2026
$2.4M
Mentoring Translational Researchers for Careers in Pediatric Global HealthK24AI113002 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FEENEY, MARGARET E · 2014 to 2023
$1.9M
Mentoring translational scientists in international infectious disease researchK24AI144048 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Bryan R Greenhouse · 2019 to 2026
$1.6M
Translational Studies of Plasmodium Falciparum Infection DynamicsK23AI076614 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GREENHOUSE, BRYAN R · 2008 to 2012
$609k
NIAID NIH HHS K23 AI076614NIAID NIH HHS K24 AI113002NIAID NIH HHS K24 AI144048NIAID NIH HHS R01 AI093615NIAID NIH HHS T32 AI007502NIAID NIH HHS U01 AI150741NIAID NIH HHS U01 AI155325NIAID NIH HHS U01 AI165527NIAID NIH HHS U19 AI089674NIAID NIH HHS U19 AI167903NIGMS NIH HHS T32 GM139791
6 · The paper itself

Abstract

The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired clinical immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by time-of-flight, that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing-at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.3 correlated with suppressed cytokine responses among monocytes of Ugandan children. Such an epigenetic signature was observed across diverse immune cell populations and not only characterized active asymptomatic parasitemia but also correlated with future long-term disease tolerance and clinical immunity when observed in uninfected children. Pseudotime analyses revealed a potential trajectory of epigenetic change that correlated with a child's age and recent parasite exposure and paralleled the acquisition of clinical immunity. Thus, our data support a model whereby exposure to

Identifiers

PMID39161730
PMCPMC11331423

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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.