Intraphagosomal Mycobacterium tuberculosis acquires iron from both extracellular transferrin and intracellular iron pools: Impact of interferon-γ and hemochromatosis

Oyebode Olakanmi, Larry S. Schlesinger, Ambar Ahmed, Bradley E. Britigan

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Mycobacterium tuberculosis multiplies within the macrophage phagosome and requires iron for growth. We examined the route(s) by which intracellular M. tuberculosis acquires iron. During intracellular growth of the virulent Erdman M. tuberculosis strain in human monocyte-derived macrophages (MDM), M. tuberculosis acquisition of 59Fe from transferrin (TF) provided extracellularly (exogenous source) was compared with acquisition when MDM were loaded with 59Fe from TF prior to M. tuberculosis infection (endogenous sources). M. tuberculosis 59Fe acquisition required viable bacteria and was similar from exogenous and endogenous sources at 24 h and greater from exogenous iron at 48 h. Interferon-γ treatment of MDM reduced 59Fe uptake from TF 51% and TF receptor expression by 34%. Despite this, intraphagosomal M. tuberculosis iron acquisition in IFN-γ-treated cells was decreased by only 30%. Macrophages from hereditary hemochromatosis patients have altered iron metabolism. Intracellular M. tuberculosis acquired markedly less iron in MDM from these individuals than in MDM from healthy donors, regardless of the iron source (exogenous and endogenous): 36 ± 3.8% and 17 ± 9.6% of control, respectively. Thus, intraphagosomal M. tuberculosis can acquire iron from both extracellular TF and endogenous macrophage sources. Acquisition of iron from macrophage cytoplasmic iron pools may be critical for the intracellular growth of M. tuberculosis. This acquisition is altered by IFN-γ treatment to a small extent, but is markedly reduced in macrophages from hemochromatosis patients.

Original languageEnglish (US)
Pages (from-to)49727-49734
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number51
DOIs
StatePublished - Dec 20 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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