Withholding iron as a cellular defence mechanism--friend or foe?
During infection one critical host defence strategy is an attempt to withhold iron from invading pathogens. This is achieved by by proinflammatory cytokines such as IL-6 inducing hepcidin. The net result of this is the removal of iron from the circulation and its sequestration within cells, including cells of the immune system such as macrophages. As macrophages are central cells for controlling infections with intracellular bacteria such as Salmonella and Mycobacteria, modulation of iron by hepcidin can lead to the provision of an ideal cellular iron source for these pathogens. Here we discuss how activation of macrophages with IFN-gamma not only up-regulates antimicrobial effector mechanisms but also modulates iron regulatory proteins such as ferroportin to reduce intracellular iron availability.
Collins
Helen L
HL
Department of Infectious Disease, Division of Immunology, Infection and Inflammatory Disease, Kings College London, London, UK. helen.collins@kcl.ac.uk
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism*; D001419:Bacteria / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D027682:Cation Transport Proteins / Q000378:metabolism*; D003573:Cytochrome b Group / Q000378:metabolism; D004198:Disease Susceptibility; D064451:Hepcidins; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D010088:Oxidoreductases / Q000378:metabolism; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D003573:Cytochrome b Group; C578702:HAMP protein, human; D064451:Hepcidins; D000098742:Ferroportin; D007371:Interferon-gamma; D007501:Iron; D010088:Oxidoreductases; C422926:CYBRD1 protein, human