Abstract
Several lines of evidence have suggested that iron is critical for Mycobacterium tuberculosis growth in macrophages. Macrophage iron loading in patients with African iron overload increases the risk of tuberculosis (TB) and may worsen TB outcome. Likewise, macrophage iron loading may contribute to an increased predisposition toward TB in HIV infection. Human genetic disorders or variations may increase the risk of TB or worsen its outcome through macrophage iron loading, including the haptoglobin 2-2 phenotype, NRAMP1 polymorphisms (at least in Africans and Asians), and possibly ferroportin 1 mutations, but not HFE hemochromatosis. Thus, the host's iron status may be an important yet underevaluated factor in TB prevention and therapy and in TB vaccine design.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Antitubercular Agents / pharmacology
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Cation Transport Proteins / genetics
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Cytokines / metabolism
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Haptoglobins / genetics
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Humans
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Iron / metabolism*
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Iron Overload / complications*
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Iron Overload / genetics
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Macrophages / chemistry
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Macrophages / metabolism*
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Macrophages / microbiology
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Mononuclear Phagocyte System / chemistry
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / growth & development*
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Mycobacterium tuberculosis / immunology
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Tuberculosis / drug therapy
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Tuberculosis / etiology*
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Tuberculosis / genetics
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Tuberculosis / metabolism
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Tuberculosis Vaccines / standards
Substances
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Antitubercular Agents
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Cation Transport Proteins
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Cytokines
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Haptoglobins
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Tuberculosis Vaccines
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metal transporting protein 1
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natural resistance-associated macrophage protein 1
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Iron