Evidence map›Paper›PMID 33665641›Full record

ArticleMed (New York, N.Y.)2021

Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.

Joe N Frost, Tiong Kit Tan, Munawar Abbas, Sarah K Wideman, Michael Bonadonna, Nicole U Stoffel, Katherine Wray, Barbara Kronsteiner, Gaby Smits, Dean R Campagna and 24 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Med (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 2% of its field
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

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Iron and the immune system.Nature reviews. Immunology · 2025
    Review
  18. Article
  19. Article
  20. Article

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 10 institutions in 6 countries.

Joe N FrostMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Tiong Kit TanMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Munawar AbbasFood and Nutritional Sciences, School of Chemistry, Food, and Pharmacy, University of Reading, Reading, UK.
Sarah K WidemanMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Michael BonadonnaDivision of Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Nicole U StoffelETH Zurich, Human Nutrition Laboratory, Institute of Food, Nutrition, and Health, Zurich, Switzerland.
Katherine WrayMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Barbara KronsteinerCentre for Tropical Medicine and Global Health, and Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Gaby SmitsCentre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Dean R CampagnaDepartment of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Tiago L DuarteInstituto de Biologia Molecular e Celular & Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.
José M LopesFaculty of Medicine (FMUP) and Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal.
Akshay ShahRadcliffe Department of Medicine, University of Oxford and John Radcliffe Hospital, Oxford, UK.
Andrew E ArmitageMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
João ArezesMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Pei Jin LimMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Alexandra E PrestonMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
David AhernMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Megan TehMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Caitlin NaylorMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Mariolina SalioMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Uzi GileadiMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Simon C AndrewsSchool of Biological Sciences, University of Reading, Reading, UK.
Susanna J DunachieCentre for Tropical Medicine and Global Health, and Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Michael B ZimmermannETH Zurich, Human Nutrition Laboratory, Institute of Food, Nutrition, and Health, Zurich, Switzerland.
Fiona R M van der KlisCentre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Vincenzo CerundoloMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Oliver BannardMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Simon J DraperThe Jenner Institute, University of Oxford, Oxford, UK.
Alain R M TownsendMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Bruno GalyDivision of Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Mark D FlemingDepartment of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Marie C LewisFood and Nutritional Sciences, School of Chemistry, Food, and Pharmacy, University of Reading, Reading, UK.
Hal DrakesmithMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
John Radcliffe Hospital · GBUniversity of Reading · GBBoston Children's Hospital · USETH Zurich · CHGerman Cancer Research Center · DEMedawar Building for Pathogen Research · GBNational Institute for Public Health and the Environment · NLi3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto · PTUniversidade do Porto · PTUniversity of Oxford · GB

Funding

Medical Research Council MC_UU_00008/10Medical Research Council MC_UU_12010/10Wellcome Trust 105654/Z/14/ZWellcome Trust 106917/Z/15/ZWellcome Trust 108869/Z/15/Z
6 · The paper itself

Abstract

backgroundHow specific nutrients influence adaptive immunity is of broad interest. Iron deficiency is the most common micronutrient deficiency worldwide and imparts a significant burden of global disease; however, its effects on immunity remain unclear.

methodsWe used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells

findingsWe show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of activated lymphocytes requires the support of enhanced iron acquisition, which is facilitated by IRP1/2 and TFRC. Accordingly, providing extra iron improved the response to vaccination in hypoferremic mice and piglets, while conversely, hypoferremic humans with chronically increased hepcidin have reduced concentrations of antibodies specific for certain pathogens. Imposing hypoferremia blunted the T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist and exacerbating lung inflammation and morbidity.

conclusionsHypoferremia, a well-conserved physiological innate response to infection, can counteract the development of adaptive immunity. This nutrient trade-off is relevant for understanding and improving immune responses to infections and vaccines in the globally common contexts of iron deficiency and inflammatory disorders.

fundingMedical Research Council, UK.

Indexed as

Iron DeficienciesIron Metabolism DisordersAnimalsHepcidinsHumansImmunity, HumoralIronMiceMice, Inbred C57BLMice, KnockoutSwineVaccinationHepcidinsIronadaptive immunityglobal healthhepcidinhypoferremiaimmunometabolisminfectioninfluenza virusironT-cellsvaccination

Identifiers

PMID33665641
PMCPMC7895906
OpenAlexW3098571299

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.