02677nas a2200421   4500008004100000022001400041245009700055210006900152260001200221300001200233490000700245520147600252653002501728653001201753653003601765653003001801653001401831653001401845653003301859653001401892653002101906653000901927653001501936653001601951653000901967653001701976653002201993653002702015653001602042653003202058100001902090700002102109700001902130700002102149700001802170700001902188856004802207       2008                        eng d  a0014-298000aInterferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium.0 aInterferongamma limits the availability of iron for intramacroph  c07/2008  a1923-360 v383 a<p>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.</p>10aAcute-Phase Proteins10aAnimals10aAntimicrobial Cationic Peptides10aCation Transport Proteins10aCell Line10aFerritins10aHeme Oxygenase (Decyclizing)10aHepcidins10aInterferon-gamma10aIron10aLipocalins10aMacrophages10aMice10aNitric Oxide10aOncogene Proteins10aSalmonella typhimurium10aTransferrin10aTumor Necrosis Factor-alpha1 aNairz, Manfred1 aFritsche, Gernot1 aBrunner, Peter1 aTalasz, Heribert1 aHantke, Klaus1 aWeiss, Günter  uhttp://www.ncbi.nlm.nih.gov/pubmed/18581323