HIV & Tuberculosis Disease: Iron balance and iron-regulatory system alterations correlate with HIV and TB disease progression

AIDSWEEKLY Plus; Monday, July 24, 2006
Staff Medical Writers

According to a recent review from England, "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," J.M. McDermid and colleagues at the University London, London School of Hygiene & Tropical Medicine wrote.

"In this review," said the authors, "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 focusing on two candidate genes, haptoglobin and NRAMPI, 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," McDermid continued, "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."

Scientists concluded that there "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."

McDermid and colleagues published the results of their research in Clinical Science (Iron and infection: effects of host iron status and the iron-regulatory genes haptoglobin and NRAMPI (SLCIIAI) on host-pathogen interactions in tuberculosis and HIV. Clin Sci (Lond), 2006;110(5):503-524).

For additional information, contact A.M. Prentice, University of London London School Hyg & Trop Med, Medical Research Council, International Nutrition Group, Keppel St., London WC1E 7HT, England.

The publisher of the journal Clinical Science can be contacted at: Portland Press Ltd., Third Floor, Eagle House, 16 Procter Street, London WC1V 6 Nx, England.

Keywords: London, England, HIV/AIDS, Tuberculosis, Iron Regulatory Genes, Host Immune Function, Iron Balance.

This article was prepared by AIDS Weekly editors from staff and other reports.

2006-07-24
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