| ironjustice@aol.com 2006-04-08, 11:29 am |
| Iron and infection: effects of host iron status and the iron-regulatory
genes haptoglobin and NRAMP1 (SLC11A1) on host-pathogen interactions in
tuberculosis and HIV.
McDermid JM, Prentice AM
Clin Sci (Lond). 2006 May ; 110(5): 503-24
There are many lines of evidence illustrating that iron plays a pivotal
role in modulating the battle for survival between mammalian hosts and
their pathogens. Each displays considerable genetic investment in a
wide range of mechanisms for acquiring and maintaining iron. These
competitive mechanisms are highly complex, existing within an
interacting matrix of absorption, transport, storage and detoxification
systems, each of which are iron-responsive and thus able to adapt to
the different phases of infection. Considerable genetic polymorphism in
some of these systems, with signals of geographic selection in the
hosts, and niche selection in the pathogens, indicates that they are
critical for species survival. In this review we briefly summarize the
role of iron in host immune function before reviewing the available
evidence that iron modulates susceptibility and disease outcomes in HIV
and TB (tuberculosis). We then examine the putative role of
iron-related host genes by focussing on two candidate genes,
haptoglobin and NRAMP1, for which there are common polymorphic variants
in humans with strong evidence of functionally distinct biochemical
phenotypes that would be predicted to influence the course of HIV and
TB infections. Finally, we examine the limited evidence so far
available that nutrient-gene interactions are likely to influence the
way in which gene variants can protect against infection. We conclude
that there is a wealth of evidence associating alterations in iron
balance and in iron-regulatory systems with disease progression, but
that many issues related to the direction of causality, mechanisms of
action and sensitivity to pharmacological intervention remain to be
elucidated. Since iron is probably the most widely prescribed compound
throughout the world, used in both preventative and treatment regimens,
a deeper understanding of the host-pathogen interactions relating to
iron constitutes an important area for both basic and clinical
research.
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Tom
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