Cell iron status influences macrophage polarization

• Published in: PloS one Vol. 13; no. 5; p. e0196921
• Main Authors: Agoro, Rafiou, Taleb, Meriem, Quesniaux, Valerie F J, Mura, Catherine
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.05.2018; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Analysis; Biology and Life Sciences; CD86 antigen; Chemokines; Cytokines; Diet; Ecology and Environmental Sciences; Ethics; Gene expression; Hepcidin; Homeostasis; Immune response; Immune system; Immunity; Immunology; Inflammation; Inflammatory response; Influence; Innate immunity; Interleukin 10; Interleukin 12; Interleukin 6; Intracellular; Iron; Iron deficiency; Life Sciences; Lipopolysaccharides; Liver; Macrophages; Major histocompatibility complex; Mammals; Medicine and Health Sciences; Metabolism; Molecular chains; NF-κB protein; Nitric-oxide synthase; Nuclear transport; Nutrient deficiency; Outcome and process assessment (Medical care); Peritoneum; Phenotypic plasticity; Polarization; Priming; Rodents; Signal transduction; Transcription factors; Translocation; Tumor necrosis factor-α; France; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196921

Macrophages play crucial roles in innate immune response and in the priming of adaptive immunity, and are characterized by their phenotypic heterogeneity and plasticity. Reprogramming intracellular metabolism in response to microenvironmental signals is required for M1/M2 macrophage polarization and function. Here we assessed the influence of iron on the polarization of the immune response in vivo and in vitro. Iron-enriched diet increased M2 marker Arg1 and Ym1 expression in liver and peritoneal macrophages, while iron deficiency decreased Arg1 expression. Under LPS-induced inflammatory conditions, low iron diet exacerbated the proinflammatory response, while the IL-12/IL-10 balance decreased with iron-rich diet, thus polarizing toward type 2 response. Indeed, in vitro macrophage iron loading reduced the basal percentage of cells expressing M1 co-stimulatory CD86 and MHC-II molecules. Further, iron loading of macrophages prevented the pro-inflammatory response induced by LPS through reduction of NF-κB p65 nuclear translocation with decreased iNOS, IL-1β, IL-6, IL-12 and TNFα expression. The increase of intracellular iron also reduced LPS-induced hepcidin gene expression and abolished ferroportin down-regulation in macrophages, in line with macrophage polarization. Thus, iron modulates the inflammatory response outcome, as elevated iron levels increased M2 phenotype and negatively regulated M1 proinflammatory LPS-induced response.