ArticleJCI insight2017
Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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.
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Who cites it
64 citing papers in PubMed, 91 citations in OpenAlex.
- Enhanced labile plasma iron in hematopoietic stem cell transplanted patients promotesBlood advances · 2019Trial
- The Gut-Iron-Immune Axis in Severe Anaemia and Bacteraemia.Nutrients · 2026Review
- 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 · 2026Review
- AnResearch square · 2026Article
- Ferroportin inhibition attenuates pulmonary hypertension in hypoxic sickle cell disease mice.Blood advances · 2026Article
- Review
- African-specific genetic loci determine iron status and risk of severe malaria and bacteremia in African children.Nature communications · 2026Article
- β-Hairpin Antimicrobial Peptides: Class Diversity and Sequence Analysis.ACS infectious diseases · 2026Review
- Metalloimmunotherapies: metal-driven regulatory networks in the immune microenvironment.Frontiers in immunology · 2026Review
- Liver as a key organ for systemic antimicrobial defense.Hepatology communications · 2025Review
- Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation.Journal of pharmaceutical analysis · 2025Review
- Hepcidin sustains Kupffer cell immune defense against bloodstream bacterial infection via gut-derived metabolites in mice.The Journal of clinical investigation · 2025Article
- Free erythrocyte protoporphyrin fluorescence as an underrecognized prognostic marker of mortality in community-acquired pneumonia.Scientific reports · 2025Article
- Iron at the crossroads of host-microbiome interactions in health and disease.Nature microbiology · 2025Review
- Essential role of hepcidin in host resistance to disseminated candidiasis.Cell reports · 2025Article
- Exploiting haem-iron dependence of nontypeableFrontiers in cellular and infection microbiology · 2025Review
- Systemic Iron Metabolism.Advances in experimental medicine and biology · 2025Review
- Low-cost in-house re-formulated brain heart infusion medium for effective planktonic growth and early detection of bloodstream bacterial pathogens.Frontiers in microbiology · 2025Article
- Biology of Anemia: A Public Health Perspective.The Journal of nutrition · 2023Article
- New Perspectives on Circulating Ferritin: Its Role in Health and Disease.Molecules (Basel, Switzerland) · 2023Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Gram-negative pneumonia is a dangerous illness, and bacterial dissemination to the bloodstream during the infection is strongly associated with death. Antibiotic resistance among the causative pathogens has resulted in diminishing treatment options against this infection. Hepcidin is the master regulator of extracellular iron availability in vertebrates, but its role in the context of host defense is undefined. We hypothesized that hepcidin-mediated depletion of extracellular iron during Gram-negative pneumonia protects the host by limiting dissemination of bacteria to the bloodstream. During experimental pneumonia, hepcidin was induced in the liver in an IL-6-dependent manner and mediated a rapid decline in plasma iron. In contrast, hepcidin-deficient mice developed a paradoxical increase in plasma iron during infection associated with profound susceptibility to bacteremia. Incubation of bacteria with iron-supplemented plasma enhanced bacterial growth in vitro, and systemic administration of iron to WT mice similarly promoted increased susceptibility to bloodstream infection. Finally, treatment with a hepcidin analogue restored hypoferremia in hepcidin-deficient hosts, mediated bacterial control, and improved outcomes. These data show hepcidin induction during pneumonia to be essential to preventing bacterial dissemination by limiting extracellular iron availability. Hepcidin agonists may represent an effective therapy for Gram-negative infections in patients with impaired hepcidin production or signaling.
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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.