An Iron-Rich Diet Decreases the Mycobacterial Burden and Correlates With Hepcidin Upregulation, Lower Levels of Proinflammatory Mediators, and Increased T-Cell Recruitment in a Model of Mycobacterium bovis Bacille Calmette-Guerin Infection
Open accessAbstract
Background: Recent evidence indicates a robust competition between the host and mycobacteria for iron acquisition during mycobacterial infection. Variable effects of iron supplementation on the susceptibility to mycobacterial infection have been reported. In this study, we revisited the effects of an experimental iron-enriched diet on Mycobacterium bovis bacille Calmette-Guerin (BCG) infection. Methods: Mice fed a standard diet or a diet moderately enriched with iron were infected with M. bovis BCG expressing green fluorescent protein. Colony-forming unit numbers, host myeloid cell counts, cell recruitment, cytokine production, and iron gene expression were determined at different stages of infection. Bone marrow-derived macrophages incubated with or without iron were also used to measure bacterial uptake, levels of inflammation markers, and iron gene expression. Results: In vivo analysis of BCG-infected mice revealed that moderate iron supplementation reduced inflammation, as measured by decreased proinflammatory cytokine levels and neutrophil recruitment and enhanced T-cell recruitment in granulomas, and decreased the bacterial load. Enhanced bacterial clearance in the liver correlated with upregulation of the gene encoding hepcidin, which is known to have antimicrobial proprieties, and with sequestration of iron in tissues. In cultured macrophages, iron supplementation induced reactive oxygen species and reduced uptake and intracellular growth of BCG. Conclusion: Moderate iron diet supplementation diminished inflammation and growth of M. bovis BCG via enhanced reactive oxygen species production, immune cell activation, and local hepcidin expression.
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Moderate iron supplementation increases T-cell recruitment to granulomas and enhances reactive oxygen species production that limits M. tuberculosis replication.
“It should be noted that moderate iron supplementation also results in increased T-cell recruitment to granulomas and enhanced reactive oxygen species production that limits M. tuberculosis replication (Agoro et al., 2017).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Agoro et al., 2017
High dietary iron weakens host defense by inhibiting macrophage interferon-γ signaling, decreasing neutrophil recruitment, and reducing pro-inflammatory cytokine expression.
“Additionally, high dietary iron weakens other arms of the host defense. Iron inhibits macrophage interferon-γ signaling, a pro-inflammatory cytokine important for producing bactericidal nitric oxide gas (Weiss et al., 1992), decreases the recruitment of neutrophils (a primary innate defense against M. tuberculosis infection), and reduces pro-inflammatory cytokine expression (Agoro et al., 2017).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Agoro et al., 2017
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Sorted by citations
Sanchez, K. K., Chen, G. Y., Schieber, A. M. P., Redford, S. E., Shokhirev, M. N., Leblanc, M., Lee, Y. M., & Ayres, J. S. (2018) · Cell · doi:10.1016/j.cell.2018.07.016 · Cited by 175 · see citing works
“In experimental studies, iron-enriched diets conferred protection against certain infections, including Helicobacter pylori and Mycobacterium bovis (Agoro et al., 2017; Beckett et al., 2016) but exacerbated infections with Salmonella (Nairz et al.”
The Impact of Dietary Transition Metals on Host-Bacterial Interactions
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- Authors
- Agoro, R., Benmerzoug, S., Rose, S., Bouyer, M., Gozzelino, R., Garcia, I., Ryffel, B., Quesniaux, V. F. J., & Mura, C.
- Affiliations
- Université d'Orléans (FR)
- Universidade Nova de Lisboa (PT)
- Corresponding author
- Mura, Catherine
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08-02
- Volume
- 216
- Issue
- 7
- Pages
- 907-918
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2739998076
- Cited by
- 22
- References
- 18
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 4
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- HAL (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- iron supplementation, iron-rich diet, Mycobacterium bovis BCG, mycobacterial infection, hepcidin, iron acquisition, inflammation, inflammatory cytokines, T cell recruitment, neutrophil recruitment, granuloma, reactive oxygen species, macrophages, bacterial clearance, iron sequestration
- MeSH terms
- Animals, Iron, Liver, Lung, Mycobacterium bovis, T-Lymphocytes, Tuberculosis, Up-Regulation, Cytokines, Iron, Dietary, Mice, Hepcidins
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