The role of iron in the immune response to bacterial infection

Abstract

My laboratory has been interested for some time in the influence of iron, a nutrient that is essential for both microbial pathogens and their mammalian hosts, on the course of infectious disease. Our studies indicate that alterations in the expression of host molecules that sequester or transport iron can have direct effects on pathogen growth and can also have an impact on the ability to mount normal immune responses. We have elucidated the mechanistic basis for some of these observations, and have started to apply our findings in strategies to control abnormalities of inflammation and iron metabolism. I will review here what we have learned about the interactions between iron and immunity and discuss the implications of the information that we have acquired.

Fig. 1

Systemic iron metabolism in mammals. Hepcidin is the key regulator of iron homeostasis. It controls the amount of iron released into the serum by phagocytes and duodenal enterocytes by modulating FPN expression on these cells. Expression of hepcidin by hepatocytes is regulated by circulating iron-transferrin levels, by iron requirements, and by inflammation

Fig. 2

Effects of macrophage FPN levels on intracellular bacterial growth and inflammatory cytokine expression. The diagram on the left depicts the effects of high FPN levels–low intracellular iron, with consequent inhibition of bacterial growth and decreased inflammatory cytokine production. The effects of low FPN are shown on the right–high intracellular iron, with consequent promotion of bacterial growth and increased inflammatory cytokine production