Evidence map›Paper›PMID 40214640›Full record

ArticleThe Journal of experimental medicine2025

Plasmodium falciparum infection induces T cell tolerance that is associated with decreased disease severity upon re-infection.

Diana Muñoz Sandoval, Florian A Bach, Alasdair Ivens, Adam C Harding, Natasha L Smith, Michalina Mazurczyk, Yrene Themistocleous, Nick J Edwards, Sarah E Silk, Jordan R Barrett and 7 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
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

17 authors.

Diana Muñoz Sandoval *Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0001-8350-3989
Florian A Bach *Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0002-0126-5516
Alasdair IvensInstitute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0002-0112-3876
Adam C HardingInstitute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0003-1479-959X
Natasha L SmithInstitute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0003-0137-3143
Michalina MazurczykWeatherall Institute of Molecular Medicine, University of Oxford , Oxford, UK.ORCID 0000-0001-7727-9036
Yrene ThemistocleousThe Jenner Institute, University of Oxford , Oxford, UK.
Nick J EdwardsThe Jenner Institute, University of Oxford , Oxford, UK.ORCID 0000-0002-7030-7839
Sarah E SilkThe Jenner Institute, University of Oxford , Oxford, UK.ORCID 0000-0003-0563-4814
Jordan R BarrettThe Jenner Institute, University of Oxford , Oxford, UK.ORCID 0000-0003-0746-1945
Graeme J M CowanInstitute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0002-1949-4253
Giorgio NapolitaniWeatherall Institute of Molecular Medicine, University of Oxford , Oxford, UK.ORCID 0000-0002-3605-6394
Nicholas J SavillInstitute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0002-9769-6168
Simon J DraperThe Jenner Institute, University of Oxford , Oxford, UK.ORCID 0000-0002-9415-1357
Angela M MinassianThe Jenner Institute, University of Oxford , Oxford, UK.ORCID 0000-0001-7832-9824
Wiebke Nahrendorf *Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0002-4503-8761
Philip J Spence *Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh, UK.ORCID 0000-0002-5506-2773

Funding

Biotechnology and Biological Sciences Research CouncilDarwin Trust of EdinburghEuropean UnionEuropean Union's Horizon 2020 733073Global Challenges Research FundHuman Infection Challenge Network for Vaccine DevelopmentJenner InstituteMedical Research CouncilNational Institute for Health Research Oxford Biomedical Research CentreRoyal Society 107668/Z/15/ZUniversity of EdinburghU.S. Agency for International Development AID-OAA-C-15-00071Wellcome TrustWellcome Trust 203764/Z/16/Z
6 · The paper itself

Abstract

Immunity to severe malaria is acquired quickly, operates independently of pathogen load, and represents a highly effective form of disease tolerance. The mechanism that underpins tolerance remains unknown. We used a human rechallenge model of falciparum malaria in which healthy adult volunteers were infected three times over a 12 mo period to track the development of disease tolerance in real-time. We found that parasitemia triggered a hardwired innate immune response that led to systemic inflammation, pyrexia, and hallmark symptoms of clinical malaria across the first three infections of life. In contrast, a single infection was sufficient to reprogram T cell activation and reduce the number and diversity of effector cells upon rechallenge. Crucially, this did not silence stem-like memory cells but instead prevented the generation of cytotoxic effectors associated with autoinflammatory disease. Tolerized hosts were thus able to prevent collateral tissue damage in the absence of antiparasite immunity.

Indexed as

Immune ToleranceMalaria, FalciparumPlasmodium falciparumReinfectionT-LymphocytesAdultFemaleHumansImmunity, InnateLymphocyte ActivationMaleParasitemiaSeverity of Illness Index

Identifiers

PMID40214640
PMCPMC11987708

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.