Iron and microbial infection

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.