Iron and innate antimicrobial immunity-Depriving the pathogen, defending the host

Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)
Manfred NairzGünter Weiss

Abstract

The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as 'nutritional immunity'. Iron metabolism and the immune response are intimately linked. In infections, the availability of iron affects both the efficacy of antimicrobial immune pathways and pathogen proliferation. However, host strategies to withhold iron from microbes vary according to the localization of pathogens: Infections with extracellular bacteria such as Staphylococcus aureus, Streptococcus, Klebsiella or Yersinia stimulate the expression of the iron-regulatory hormone hepcidin which targets the cellular iron-exporter ferroportin-1 causing its internalization and blockade of iron egress from absorptive enterocytes in the duodenum and iron-recycling macrophages. This mechanism disrupts both routes of iron delivery to the circulation, contributes to iron sequestration in the mononuclear phagocyte system and mediates the hypoferraemia of th...Continue Reading

Citations

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