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

Rafiou Agoro, Sulayman Benmerzoug, Stéphanie Rose, Mélanie Bouyer, Raffaella Gozzelino, Irene Garcia, Bernhard Ryffel, Valerie F J Quesniaux, Catherine Mura

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)907-918
Number of pages12
JournalJournal of Infectious Diseases
Volume216
Issue number7
DOIs
Publication statusPublished - 17 Oct 2017

Keywords

  • Journal Article

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