Dendritic cell–derived hepcidin sequesters iron from the microbiota to promote mucosal healing

Bessman, Nicholas J.; Mathieu, Jacques; Renassia, Cyril; Zhou, Lei; Fung, Thomas C.; Fernandez, Keith Conrad; Austin, Christine; Møeller, Jesper Bonnet; Zumerle, Sara; Louis, Sabine; Vaulont, Sophie; Ajami, Nadim J.; Sokol, Harry; Putzel, Gregory G.; Arvedson, Tara; Sockolow, Robbyn; Lakhal‐Littleton, Samira; Cloonan, Suzanne M.; Arora, Manish; Peyssonnaux, Carole; Sonnenberg, Gregory F.

doi:10.1126/science.aau6481

Cited by 96 publications

(71 citation statements)

References 30 publications

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“…Several lines of evidence have established a link between inflammation and oxidative stress ( Khomich et al, 2018 , van den Brand et al, 2014 ) . In this context, we have shown that hepcidin, the key iron regulatory molecule, plays a major role during inflammatory processes ( Bessman et al, 2020 ). We also addressed the role and management of a dysregulated iron state in COVID-19 pathogenesis ( Edeas et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

et al. 2020

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Highlights Mitochondria are the hub of cellular oxidative homeostasis. Mitochondria are the major source of reactive oxygen species (ROS). Extracellular mitochondria are found in blood, in circulating platelets and vesicles. COVID-19 pathogenesis is aggravated by the hyper- inflammatory state. Inflammation activates events leading to microbiota & mitochondrial oxidative damage. Mitochondrial damage contributes to coagulopathy, ferroptosis & microbial dysbiosis. Blood & platelet mitochondria dysfunction may accelerate systemic coagulopathy events. Targeting mitochondria dysfunction may provide useful therapeutic strategies against COVID-19 pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

et al. 2020

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“…Iron efflux from cells is critical for body iron homeostasis and is negatively controlled by hepcidin, a peptide hormone that inactivates ferroportin in macrophages, enterocytes and other target cells [ 8 ] ( Figure 1 ). Circulating hepcidin is synthesized by hepatocytes in the liver; however, hepcidin is also locally produced in other tissues and appears to have critical cell-autonomous functions [ 9 , 10 , 11 ]. The hepcidin-encoding HAMP gene is primarily induced in response to iron or inflammatory signals [ 8 ].…”

Section: Systemic Iron Metabolismmentioning

confidence: 99%

Regulatory Connections between Iron and Glucose Metabolism

Fillebeen

Lam

Chow

et al. 2020

IJMS

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Iron is essential for energy metabolism, and states of iron deficiency or excess are detrimental for organisms and cells. Therefore, iron and carbohydrate metabolism are tightly regulated. Serum iron and glucose levels are subjected to hormonal regulation by hepcidin and insulin, respectively. Hepcidin is a liver-derived peptide hormone that inactivates the iron exporter ferroportin in target cells, thereby limiting iron efflux to the bloodstream. Insulin is a protein hormone secreted from pancreatic β-cells that stimulates glucose uptake and metabolism via insulin receptor signaling. There is increasing evidence that systemic, but also cellular iron and glucose metabolic pathways are interconnected. This review article presents relevant data derived primarily from mouse models and biochemical studies. In addition, it discusses iron and glucose metabolism in the context of human disease.

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“…188,189 Conversely, iron-deficient diets in experimental systems seem to favour the growth of protective microorganisms. 107,166…”

Section: Targeting the Pathogenmentioning

confidence: 99%

The battle for iron in enteric infections

et al. 2020

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Iron is an essential element for almost all living organisms, but can be extremely toxic in high concentrations. All organisms must therefore employ homeostatic mechanisms to finely regulate iron uptake, usage and storage in the face of dynamic environmental conditions. The critical step in mammalian systemic iron homeostasis is the fine regulation of dietary iron absorption. However, as the gastrointestinal system is also home to >10 14 bacteria, all of which engage in their own programmes of iron homeostasis, the gut represents an anatomical location where the interkingdom fight for iron is never-ending. Here, we explore the molecular mechanisms of, and interactions between, host and bacterial iron homeostasis in the gastrointestinal tract. We first detail how mammalian systemic and cellular iron homeostasis influences gastrointestinal iron availability. We then focus on two important human pathogens, Salmonella and Clostridia; despite their differences, they exemplify how a bacterial pathogen must navigate and exploit this web of iron homeostasis interactions to avoid host nutritional immunity and replicate successfully. We then reciprocally explore how iron availability interacts with the gastrointestinal microbiota, and the consequences of this on mammalian physiology and pathogen iron acquisition. Finally, we address how understanding the battle for iron in the gastrointestinal tract might inform clinical practice and inspire new treatments for important diseases.

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Dendritic cell–derived hepcidin sequesters iron from the microbiota to promote mucosal healing

Cited by 96 publications

References 30 publications

Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

Regulatory Connections between Iron and Glucose Metabolism

The battle for iron in enteric infections

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