Iron and the immune system

Ward, Roberta J.; Crichton, Robert R.; Taylor, Dave; Corte, Laura Della; Srai, Surjit Kaila; Dexter, David T.

doi:10.1007/s00702-010-0479-3

Cited by 113 publications

(99 citation statements)

References 55 publications

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“…Iron is essential for the production of ROS, and it may be through hepcidin's action that iron is accumulated within cells involved in oxidative burst, but the role of hepcidin in this process has not been studied in depth. Iron status and intracellular macrophage iron levels affect the efficiency of the oxidative burst (38). In summary, the literature reviewed here indicates the importance of maintaining an optimal iron balance specific to the type of infection and emphasizes the crucial role hepcidin plays in regulation of the immune response, starting with innate immunity but also, as more recently demonstrated, for adaptive immunity.…”

Section: Current Status Of Knowledgementioning

confidence: 99%

“…These ROS created within immune cells, mainly neutrophils and macrophages, are released into phagosomes containing the engulfed or intracellular pathogen (38). Iron is essential for the production of ROS, and it may be through hepcidin's action that iron is accumulated within cells involved in oxidative burst, but the role of hepcidin in this process has not been studied in depth.…”

Section: Current Status Of Knowledgementioning

confidence: 99%

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Iron Biology, Immunology, Aging, and Obesity: Four Fields Connected by the Small Peptide Hormone Hepcidin

Dao

Meydani

2013

Advances in Nutrition

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Iron status and immune response become impaired in situations that involve chronic inflammation, such as obesity or aging. Little is known, however, about the additional burden that obesity may place on the iron status and immune response in the elderly. This question is relevant given the rising numbers of elderly obese (BMI >30 kg/m 2 ) individuals and the high prevalence of iron deficiency worldwide. Iron is necessary for proper function of both the innate and adaptive immune system. Hepcidin, a peptide hormone that regulates cellular iron export, is essential for the maintenance of iron homeostasis. Therefore, since immune cells require iron for proper function hepcidin may also play an important role in immune response. In this review, we summarize the evidence for hepcidin as a link between the fields of gerontology, obesity, iron biology, and immunology. We also identify several gaps in knowledge and unanswered questions pertaining to iron homeostasis and immunity in obese populations. Finally, we review studies that have shown the impact of weight loss, focusing on calorie restriction, iron homeostasis, and immunity. These studies are important both in elucidating mechanistic links between obesity and health impairments and identifying possible approaches to target immune impairment and iron deficiency as comorbidities of obesity.

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Section: Current Status Of Knowledgementioning

confidence: 99%

Section: Current Status Of Knowledgementioning

confidence: 99%

Iron Biology, Immunology, Aging, and Obesity: Four Fields Connected by the Small Peptide Hormone Hepcidin

Dao

Meydani

2013

Advances in Nutrition

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“…1 Most pathogens require iron for proliferation and full virulence. The innate immune system fights infections by sequestration of iron in macrophages of the reticuloendothelial system.…”

Section: Introductionmentioning

confidence: 99%

A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia

Guida

Altamura

Klein

et al. 2015

Blood

148

131

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Key Points• Stimulation of Toll-like receptors 2 and 6 reduces ferroportin expression in mouse macrophages by hepcidin-independent mechanism(s).• Reduced expression of ferroportin in macrophages that recycle iron from red cells is sufficient to rapidly induce hypoferremia in mice.Regulation of iron metabolism and innate immunity are tightly interlinked. The acute phase response to infection and inflammation induces alterations in iron homeostasis that reduce iron supplies to pathogens. The iron hormone hepcidin is activated by such stimuli causing degradation of the iron exporter ferroportin and reduced iron release from macrophages, suggesting that hepcidin is the crucial effector of inflammatory hypoferremia. Here, we report the discovery of an acute inflammatory condition that is mediated by Toll-like receptors 2 and 6 (TLR2 and TLR6) and which induces hypoferremia in mice injected with TLR ligands. Stimulation of TLR2/TLR6 triggers profound decreases in ferroportin messenger RNA and protein expression in bone marrow-derived macrophages, liver, and spleen of mice without changing hepcidin expression. Furthermore, C326S ferroportin mutant mice with a disrupted hepcidin/ferroportin regulatory circuitry respond to injection of the TLR2/6 ligands FSL1 or PAM3CSK4 by ferroportin downregulation and a reduction of serum iron levels. Our findings challenge the prevailing role of hepcidin in hypoferremia and suggest that rapid hepcidin-independent ferroportin downregulation in the major sites of iron recycling may represent a first-line response to restrict iron access for numerous pathogens. (Blood. 2015;125(14): [2265][2266][2267][2268][2269][2270][2271][2272][2273][2274][2275] IntroductionIron plays a central role in host-pathogen interactions.1 Most pathogens require iron for proliferation and full virulence. The innate immune system fights infections by sequestration of iron in macrophages of the reticuloendothelial system. The resulting hypoferremia represents a major host defense strategy and promotes anemia of inflammation, a form of anemia commonly associated with infectious and inflammatory conditions as well as cancer. Toll-like receptors (TLRs) are key sensors of the innate immune system.3 They recognize pathogen-associated molecular patterns (PAMPs) and control the hypoferremic host response. Lipopolysaccharide (LPS) is a cell wall component of gram-negative bacteria recognized by TLR4. LPS injection into mice causes the release of proinflammatory cytokines and triggers a wellcharacterized acute phase response including induction of the hepatic iron hormone hepcidin 4-6 by interleukin-6 (IL-6). 7,8 Hepcidin binds to and causes internalization and degradation of the iron exporter ferroportin, which limits iron release from iron-exporting cells such as macrophages, hepatocytes, and duodenal enterocytes. Diminished iron export from macrophages that recycle iron from senescent red cells rapidly induces hypoferremia due to the high iron demand of erythropoiesis. 10,11 Excess levels of hepcidin have been recog...

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“…Under normal conditions NFkappaB is present in the cytoplasm in an inactive state bound to the inhibitory protein IkappaB (IkB). decreases in IL-6 will diminish hepcidin secretion thereby preventing the internaliation of iron via the interaction of hepcidin with ferroportin [45].…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro

Ward

Lallemand

Witte

et al. 2011

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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Iron and the immune system

Cited by 113 publications

References 55 publications

Iron Biology, Immunology, Aging, and Obesity: Four Fields Connected by the Small Peptide Hormone Hepcidin

Iron Biology, Immunology, Aging, and Obesity: Four Fields Connected by the Small Peptide Hormone Hepcidin

A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro

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