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
Volume38
Issue7
Pagination1923-36
Date Published07/2008
ISSN0014-2980
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
Abstract

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.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/18581323
DOI10.1002/eji.200738056
Alternate JournalEur. J. Immunol.
PubMed ID18581323

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