Metabolic requirements of NK cells during the acute response against retroviral infection

Littwitz-Salomon, Elisabeth; Moreira, Diana; Frost, J. E. F.; Choi, Chloe; Liou, Kevin T; Ahern, David K.; O’Shaughnessy, Simon; Wagner, Bernd; Biron, Christine A.; Drakesmith, Hal; Dittmer, Ulf; Finlay, David K.

doi:10.1038/s41467-021-25715-z

Cited by 42 publications

(40 citation statements)

References 65 publications

(116 reference statements)

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“…Moreover, systematic low iron level influenced by hepcidin resulted in the suppression of NK cell activation and production of IFN-γ. Besides, they also showed that sufficient serum iron is critical to the metabolism of NK cells and their activity against virus infection ( 46 ). Accordingly, iron plays a pivotal role not only in the development and proliferation but also in the activation and function of NK cells when virus infection occurred.…”

Section: Iron and Nk Cellsmentioning

confidence: 99%

“…Cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF) produced by NK cells not only activate immune response but also make NK cells become sensitive to other cytokines (e.g., interleukin-2, IL-12, IL-15 and IL-18) ( 42 , 43 ). Activated NK cells increase expression of transferrin receptor (CD71) ( 44 , 45 ), whereas iron deficiency results in a lose function of NK cells ( 46 ). All of these indicate that iron is indispensable in the activation of NK cells.…”

Section: Iron and Nk Cellsmentioning

confidence: 99%

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Iron Metabolism and Immune Regulation

et al. 2022

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Iron is a critical element for living cells in terrestrial life. Although iron metabolism is strictly controlled in the body, disturbance of iron homeostasis under certain type of condition leads to innate and adaptive immune response. In innate immunity, iron regulates macrophage polarizations, neutrophils recruitment, and NK cells activity. In adaptive immunity, iron had an effect on the activation and differentiation of Th1, Th2, and Th17 and CTL, and antibody response in B cells. In this review, we focused on iron and immune regulation and listed the specific role of iron in macrophage polarization, T-cell activation, and B-cells antibody response. In addition, correlations between iron and several diseases such as cancer and aging degenerative diseases and some therapeutic strategies targeting those diseases are also discussed.

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Section: Iron and Nk Cellsmentioning

confidence: 99%

Section: Iron and Nk Cellsmentioning

confidence: 99%

Iron Metabolism and Immune Regulation

et al. 2022

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“…Neutrophils, monocytes/macrophages ( 246 , 247 ) and NK cells ( 248 ) use iron to combat pathogens. During intracellular infection, they release iron-loaded lactoferrin into their phagocytic vacuoles where ferrous iron functions as a catalyst of the Haber-Weiss reaction, generating reactive oxygen species (ROS) ( 249 ).…”

Section: Immune Cells Under Iron-deficient Conditionsmentioning

confidence: 99%

Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores

Roth‐Walter

2022

Front. Allergy

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Although iron is one of the most abundant elements on earth, about a third of the world's population are affected by iron deficiency. Main drivers of iron deficiency are beside the chronic lack of dietary iron, a hampered uptake machinery as a result of immune activation. Macrophages are the principal cells distributing iron in the human body with their iron restriction skewing these cells to a more pro-inflammatory state. Consequently, iron deficiency has a pronounced impact on immune cells, favoring Th2-cell survival, immunoglobulin class switching and primes mast cells for degranulation. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both children and adults with allergy are more likely to have anemia. In contrast, an improved iron status seems to protect against allergy development. Here, the most important interconnections between iron metabolism and allergies, the effect of iron deprivation on distinct immune cell types, as well as the pathophysiology in atopic diseases are summarized. Although the main focus will be humans, we also compare them with innate defense and iron sequestration strategies of microbes, given, particularly, attention to catechol-siderophores. Similarly, the defense and nutritional strategies in plants with their inducible systemic acquired resistance by salicylic acid, which further leads to synthesis of flavonoids as well as pathogenesis-related proteins, will be elaborated as both are very important for understanding the etiology of allergic diseases. Many allergens, such as lipocalins and the pathogenesis-related proteins, are able to bind iron and either deprive or supply iron to immune cells. Thus, a locally induced iron deficiency will result in immune activation and allergic sensitization. However, the same proteins such as the whey protein beta-lactoglobulin can also transport this precious micronutrient to the host immune cells (holoBLG) and hinder their activation, promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holoBLG as a food for special medical purposes, leading to a reduction in the allergic symptom burden. Supplementation with nutrient-carrying lipocalin proteins can circumvent the mucosal block and nourish selectively immune cells, therefore representing a new dietary and causative approach to compensate for functional iron deficiency in allergy sufferers.

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“…Hepcidin blocks iron recycling by hemophagocytic macrophages and iron absorption by duodenal enterocytes, suppressing serum iron concentrations (4). This response can protect against certain siderophilic bacterial pathogens, constituting an acute "nutritional immune" mechanism but, if prolonged, leads to inflammatory anemia and can inhibit proliferative lymphocyte responses to immunization and infection (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Plasma iron controls neutrophil production and function

et al. 2022

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Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types. Accordingly in mice, hepcidin-mediated hypoferremia substantially reduced numbers of granulocytes but not monocytes, lymphocytes, or dendritic cells. Neutrophil rebound after anti-Gr-1–induced neutropenia was blunted during hypoferremia but was rescued by supplemental iron. Similarly, hypoferremia markedly inhibited pharmacologically stimulated granulopoiesis mediated by granulocyte colony-stimulating factor and inflammation-induced accumulation of neutrophils in the spleen and peritoneal cavity. Furthermore, hypoferremia specifically altered neutrophil effector functions, suppressing antibacterial mechanisms but enhancing mitochondrial reactive oxygen species–dependent NETosis associated with chronic inflammation. Notably, antagonizing endogenous hepcidin during acute inflammation enhanced production of neutrophils. We propose plasma iron modulates the profile of innate immunity by controlling monocyte-to-neutrophil ratio and neutrophil activity in a therapeutically targetable system.

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Metabolic requirements of NK cells during the acute response against retroviral infection

Cited by 42 publications

References 65 publications

Iron Metabolism and Immune Regulation

Iron Metabolism and Immune Regulation

Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores

Plasma iron controls neutrophil production and function

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