ArticleThe Journal of experimental medicine2002
Correction of the iron overload defect in beta-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 194 citations in OpenAlex.
- Iron status predicts treatment failure and mortality in tuberculosis patients: a prospective cohort study from Dar es Salaam, Tanzania.PloS one · 2012Trial
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- Review
- Parenteral iron-Does it increase infection risk?Vox sanguinis · 2026Review
- CD8+ lymphocytes in immunity against tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Ferroptosis is important forVirulence · 2025Article
- Dysregulation of the JNK signaling pathway in tuberculosis: mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Iron, Hepcidin, and Immunity.Advances in experimental medicine and biology · 2025Review
- Decoding differentially expressed genes to identify potential immunity associated biomarkers in Tuberculosis: An integrative bioinformatics approach.Biochemistry and biophysics reports · 2024Article
- Solanum lycopersicum heme-binding protein 2 as a potent antimicrobial weapon against plant pathogens.Scientific reports · 2023Article
- Trace metal elements: a bridge between host and intestinal microorganisms.Science China. Life sciences · 2023Review
- Mycobacterium tuberculosis hijacks host TRIM21- and NCOA4-dependent ferritinophagy to enhance intracellular growth.The Journal of clinical investigation · 2023Article
- Iron Status and Supplementation during Tuberculosis.Microorganisms · 2023Review
- Immune cell interactions in tuberculosis.Cell · 2022Review
- Mycobacteria-host interactions in human bronchiolar airway organoids.Molecular microbiology · 2022Article
- Biting the hand that feeds: Metabolic determinants of cell fate during infection.Frontiers in immunology · 2022Review
- The link between ferroptosis and airway inflammatory diseases: A novel target for treatment.Frontiers in molecular biosciences · 2022Review
- Non-heme iron overload impairs monocyte to macrophage differentiationFrontiers in immunology · 2022Article
- Article
- The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG.International journal of molecular sciences · 2021Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. beta-2-microglobulin (beta2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)-restricted CD8 T cells in protection against M. tuberculosis. However, beta2m associates with a number of MHC-I-like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, beta2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in beta2m-KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I-KO mice. In parallel, the generation of nitric oxide impaired in beta2m-KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the increased susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
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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.