Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis

A Catharine Ross, A Catharine Ross

Abstract

Inflammation has a major impact on iron homeostasis. This review focuses on acute and chronic inflammation as it affects iron trafficking and, as a result, the availability of this essential micronutrient to the host. In situations of microbial infection, not only the host is affected but also the offending microorganisms, which, in general, not only require iron for their own growth but have evolved mechanisms to obtain it from the infected host. Key players in mammalian iron trafficking include several types of cells important to iron acquisition, homeostasis, and hematopoiesis (enterocytes, hepatocytes, macrophages, hematopoietic cells, and in the case of pregnancy, placental syncytiotrophoblast cells) and several forms of chaperone proteins, including, for nonheme iron, the transport protein transferrin and the intracellular iron-storage protein ferritin, and for heme iron, the chaperone proteins haptoglobin and hemopexin. Additional key players are the cell membrane-associated iron transporters, particularly ferroportin (FPN), the only protein known to modulate iron export from cells, and finally, the iron-regulatory hormone hepcidin, which, in addition to having antibacterial activity, regulates the functions of FPN. Interestingly, the impact of infection on iron homeostasis differs among pathogens whose mode of infection is mainly intracellular or extracellular. Understanding how inflammation affects each of these processes may be crucial for understanding how inflammation affects iron status, indicators of iron sufficiency, and iron supplementation during inflammation and how it may potentially result in a beneficial or detrimental impact on the host.

Keywords: C-reactive protein; acute phase response; ferroportin; hepatocyte; hepcidin; infancy; intra- and extracellular pathogens; macrophage; pregnancy.

© 2017 American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Schematic of pathway from initial insult to the induction of the AP response. See Kilicarslan et al. (24) and Trautwein et al. (31) for reviews of AP proteins. AGP, α1-acid glycoprotein; AP, acute phase; CRP, C-reactive protein; IFN, interferon.
FIGURE 2
FIGURE 2
Schematic of differential adaptive responses to segregate iron from microbes in the situation with extracellular infectious agents in which sequestration of iron intracellularly generally favors the host’s response (A) and with intracellular infectious agents in which removal of iron from the cell generally favors the host’s response to infection (B). (See references 4 and 5 for additional information). FPN, ferroportin.

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