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Systemic and cellular consequences of macrophage control of iron metabolism
S Recalcati1, M Locati, G Cairo
1Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
Abstract:
Iron is necessary for both mammalian cells and microorganisms, which fiercely compete for this essential nutrient. Accordingly, macrophages exploit the denial of iron from microbial pathogens as an important strategy to accomplish their key role in innate immunity and host defense. Macrophages employ multiple mechanisms to accumulate iron and thus contain microbial infections, but this may come at a price. In particular, at the systemic level iron sequestration in the reticuloendothelial cells can lead to the development of anemia of chronic disease. At the local level, iron sequestration in macrophages, which is targeted to extracellular invaders, can in turn favor intracellular pathogens. Moreover, iron accumulation can per se promote pro-inflammatory activation of macrophages and consequently contribute to maintain the process of inflammation, without resolution. Finally, the peculiar iron trafficking that characterizes alternatively polarized macrophages can influence neighboring cells in the microenvironment and impact on the resolution phase of inflammation. In this review, we describe the role of macrophages in iron metabolism in the context of host defense and iron balance.
Insights
Macrophages control iron to fight infection, but this can cause anemia and inflammation. Their iron handling impacts immune responses and disease resolution, highlighting a complex balance in host defense.
Area of Science:
- Immunology
- Cell Biology
- Host-Pathogen Interactions
Background:
- Iron is essential for mammalian cells and microorganisms, leading to competition.
- Macrophages play a crucial role in innate immunity by limiting pathogen access to iron.
- Iron dysregulation in macrophages can lead to detrimental conditions like anemia of chronic disease and chronic inflammation.
Purpose of the Study:
- To review the multifaceted role of macrophages in iron metabolism.
- To explore how macrophages' iron handling impacts host defense against pathogens.
- To discuss the implications of macrophage iron metabolism in inflammation and disease.
Main Methods:
- This is a review article, synthesizing existing research on macrophage iron metabolism.
- The review analyzes mechanisms of iron accumulation and trafficking in macrophages.
- It examines the consequences of altered iron levels on macrophage function and the microenvironment.
Main Results:
- Macrophages sequester iron to limit microbial growth, a key immune strategy.
- Systemic iron sequestration can cause anemia of chronic disease.
- Local iron accumulation in macrophages can paradoxically favor intracellular pathogens and promote inflammation.
Conclusions:
- Macrophage iron metabolism is critical for host defense but carries risks of anemia and inflammation.
- Altered iron trafficking in alternatively polarized macrophages influences the inflammatory microenvironment and resolution.
- Understanding macrophage iron dynamics is vital for managing infections and inflammatory diseases.
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