%0 Journal Article %J Eur J Immunol %D 2008 %T Interferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium. %A Nairz, Manfred %A Fritsche, Gernot %A Peter Brunner %A Talasz, Heribert %A Hantke, Klaus %A Weiss, Günter %K Acute-Phase Proteins %K Animals %K Antimicrobial Cationic Peptides %K Cation Transport Proteins %K Cell Line %K Ferritins %K Heme Oxygenase (Decyclizing) %K Hepcidins %K Interferon-gamma %K Iron %K Lipocalins %K Macrophages %K Mice %K Nitric Oxide %K Oncogene Proteins %K Salmonella typhimurium %K Transferrin %K Tumor Necrosis Factor-alpha %X

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.

%B Eur J Immunol %V 38 %P 1923-36 %8 07/2008 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/18581323 %N 7 %R 10.1002/eji.200738056