Interferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium.

TitleInterferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium.
Publication TypeJournal Article
Year of Publication2008
AuthorsNairz, M, Fritsche, G, Brunner, P, Talasz, H, Hantke, K, Weiss, G
JournalEur J Immunol
Date Published07/2008
KeywordsAcute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Cation Transport Proteins, Cell Line, Ferritins, Heme Oxygenase (Decyclizing), Hepcidins, Interferon-gamma, Iron, Lipocalins, Macrophages, Mice, Nitric Oxide, Oncogene Proteins, Salmonella typhimurium, Transferrin, Tumor Necrosis Factor-alpha

In stimulating effector functions of mononuclear phagocytes, IFN-gamma is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-gamma is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-gamma on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-gamma caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-gamma exerting a super-inducing effect. This observed regulatory impact of IFN-gamma reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-alpha production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-gamma concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity.

Alternate JournalEur. J. Immunol.
PubMed ID18581323

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