Among all the nutrients, iron stands out as having a particularly crucial role in mediating host-pathogen interactions.
- In animals, evidence for this comes from the diversity of their methods of iron sequestration and from their ability to further deprive invading organisms of iron by depleting plasma iron during the APR (acute-phase response).
- In pathogens, the strongest evidence comes from the high degree of genomic investment in systems for iron acquisition, the vast range of such systems and their very low iron-binding constants which permit them to be effective even in highly iron-depleted environments.
At first sight the suggestion that iron lies at the centre of an eons-long battle between hosts and their pathogens is surprising, since iron is the second most abundant element on the earth's crust. The explanation lies in a combination of the extreme usefulness of the redox potentials of the ferrous (Fe2+)/ferric (Fe3+) switch (which makes it widely used in enzymic and signalling systems), and the fact that most iron exists in a highly insoluble oxidized state (Fe3+).
Both iron excess and deficiency favour infections
Bacterial and protozoarian strategies
Trypanosoma brucei
The transferrin receptor of Trypanosoma brucei is encoded by genes located in different expression sites. The various expression sites encode slightly different transferrin receptors, which differ substantially in their affinity for transferrin of different host species.
The significance of transferrin receptor variation in Trypanosoma brucei 2003
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Papers Transferrin Receptor Trypanosoma brucei
Viral strategies
HIV
HIV inhibits iron efflux from the cell via the Nef protein
Alain Townsend Molecular control of human iron homeostasis, and interactions of HIV with cellular iron metabolism.
Host strategies
- transferrin
- haptoglobin
- ferritin
Acute Phase Proteins function
Haptoglobin binds hemoglobin
Lactoferrin binds iron
Transferrin binds iron
Ferritin segregates iron (ca 1000/1500 atoms x molecule)
NRAMP1 (SLC11A1) polymorphism
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 2006
In this review, we summarize current knowledge on the relationships between iron and two of the leading infectious causes of death in humankind: HIV and TB (tuberculosis). We examine the relationships both in terms of cause (i.e. the question of whether positive or negative perturbations in iron status affect susceptibility to disease and clinical progression), and in terms of effect (i.e. the pathological consequences of infection on iron homoeostasis). We also examine whether variants in host genes may influence these outcomes. At present, the evidence for gene-nutrient interactions is somewhat limited, so we focus on just two candidate genes that have been examined in some detail:
- the haemoglobin-binding acute-phase protein, Hp (haptoglobin)
- the divalent-cation transporter from the phagosome membrane of the macrophage NRAMP1 [natural-resistance-associated macrophage protein-1; now known as SLC11A1 (solute carrier family 11, member 1).
Specific infections in which a role for NRAMP1 polymorphism has been demonstrated
Open Questions
Haptoglobin: details
"Hemopexin.: details":
"Lactoferrin.: details":
"Transferrrin.: details":
In the "modern" oxygen-rich environment, iron is highly insoluble and has low bioavailability despite its abundance, making it the subject of fierce competition between a host and its pathogens
NRAMP, TBC, HIV
Pathways of Skeletal Muscle Atrophy: HIV as a Model System?
The Fe button below will take you to the iron cycle, allowing you to see the entire cycle as a whole.
Insulin and iron metabolism
Iron metabolism
Iron and cardiovascular disease
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