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Iron and microbial infection

A Correction to this article was published on 01 March 2005

Key Points

  • Iron is an essential element for all living organisms, but is of low accessibility to both micro- and macroorganisms.

  • The competition between pathogens and their hosts for iron has shaped the evolution of both pathogen survival strategies in the host, as well as host microbicidal defence mechanisms.

  • In host defence, iron is involved in the production of reactive oxygen and nitrogen intermediates.

  • Iron uptake and metabolism in the mammalian host is a well-controlled system that involves various genes and molecules, including hepcidin, transferrin, the transferrin receptor, the divalent-metal transporter-1, ferroportin, natural resistance-associated macrophage protein-1 and ferritin, which are described in this review. Mutations in some of these genes lead to iron overload.

  • Pathogens have evolved to dwell in specific niches within the host/host cell and to access iron from host sources. For example, mycobacteria survive in the early endosomes of macrophages where they interact with the host iron-transfer system.

  • Iron overload favours certain infections, including tuberculosis in humans as well as in animal models. Iron overload supports the growth of mycobacteria and accelerates the development of tuberculosis in humans and mice.

  • Iron is also a modulator of both innate as well as acquired immunity.

  • In conclusion, studies that focus on the important role of iron in host–pathogen interactions should foster the development of new intervention strategies to improve global health.

Abstract

The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. It is also a pivotal component of the innate immune response through its role in the generation of toxic oxygen and nitrogen intermediates. During evolution, the shared requirement of micro- and macroorganisms for this important nutrient has shaped the pathogen–host relationship. Here, we discuss how pathogens compete with the host for iron, and also how the host uses iron to counteract this threat.

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Figure 1: The niches of host-cell-associated microorganisms.
Figure 2: Iron metabolism in the host.
Figure 3: Iron metabolism and infection.

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Acknowledgements

Financial support was provided to S.H.E.K and U.E.S. by the Deutsche Forschungsgemeinschaft.The authors thank L. Fehlig for wonderful help with the figures and J. Koth for expert secretarial assistance.

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Correspondence to Stefan H. E. Kaufmann.

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DATABASES

Entrez

bfrA

ferroportin-1

HFE

Nramp1

SwissProt

CD163

DCYTB

DMT1

FepA

FepB

ferroportin

IdeR

TFR2

TonB

FURTHER INFORMATION

Stefan H. E. Kaufmann's laboratory

Glossary

DEFENSINS

Small basic peptides produced by immune cells that mediate their microbicidal effects by damaging bacterial membranes.

β-2-MICROGLOBULIN

(β2m). A 12-kDa protein that is non-covalently associated with MHC class-I molecules and their homologues — CD1 and HFE.

EARLY ENDOSOME

Early stage of an intracellular vesicle after endocytosis, characterized by the presence of the transferrin receptor and a mildly acidic pH.

LATE ENDOSOME

Later stage of the endosome, characterized by the presence of hydrolytic enzymes and an acidic pH.

SIDEROPHORES

Low-molecular-weight molecules that sequester extracellular iron for bacterial uptake.

LYME DISEASE

A disease transmitted by ticks that presents with inflammation in the skin, joints heart and/or nervous system.

ABC-TRANSPORTER

Member of a membrane-spanning transporter protein family that contains an ATP-binding cassette.

TRANSCRIPTOME ANALYSIS

Analysis of the global gene expression of a cell by identification of all the messenger RNA present in the cell.

NATURAL KILLER (NK) T CELLS

A small subset of T cells that express markers of both NKcells and T cells. They express a T-cell receptor of limited diversity and are restricted by CD1d.

BIOFILM

A dense layer of bacteria in which the bacterial cells are enclosed by an extracellular matrix.

CYSTIC FIBROSIS

An autosomal recessive disease characterized by pulmonary pathology and dysfunction of exocrine glands.

CYTOKINES

Biologically active molecules that are released by cells (mainly leukocytes) and that modulate the function of other cells by binding to specific receptors.

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Schaible, U., Kaufmann, S. Iron and microbial infection. Nat Rev Microbiol 2, 946–953 (2004). https://doi.org/10.1038/nrmicro1046

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