title: Intraphagosomal Mycobacterium tuberculosis acquires iron from both extracellular transferrin and intracellular iron pools. Impact of interferon-gamma and hemochromatosis.
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 (59)Fe from transferrin (TF) provided extracellularly (exogenous source) was compared with acquisition when MDM were loaded with (59)Fe from TF prior to M. tuberculosis infection (endogenous sources). M. tuberculosis (59)Fe acquisition required viable bacteria and was similar from exogenous and endogenous sources at 24 h and greater from exogenous iron at 48 h. Interferon-gamma treatment of MDM reduced (59)Fe uptake from TF 51% and TF receptor expression by 34%. Despite this, intraphagosomal M. tuberculosis iron acquisition in IFN-gamma-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-gamma treatment to a small extent, but is markedly reduced in macrophages from hemochromatosis patients.
authors.affiliation: Department of Internal Medicine and Research Service, Veteran Affairs Medical Center-Iowa City, Iowa City, IA 52246, USA.
authors.forename: Oyebode
authors.initials: O
authors.lastname: Olakanmi
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
authors.forename: Ambar
authors.initials: A
authors.lastname: Ahmed
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Britigan
mesh_terms: D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005293:Ferritins / Q000378:metabolism; D006432:Hemochromatosis / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000096:biosynthesis; D013997:Time Factors; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011990:Receptors, Transferrin; D014168:Transferrin; D007371:Interferon-gamma; D005293:Ferritins; D007501:Iron