Interferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium
Abstract number: P957
Nairz M., Fritsche G., Mair S., Theurl M., Theurl I., Schroll A., Brunner P., Hantke K., Weiss G.
Objectives: In stimulating effector functions of mononuclear phagocytes, interferon-gamma (IFN-g) is of pivotal importance in host defence against intramacrophage pathogens including salmonellae. As the activity of IFN-g is modulated by iron and since a sufficient availability of iron is essential for the growth and proliferation of pathogens, we investigated the regulatory effects of IFN-g on iron homeostasis and immune function in murine macrophages infected with Salmonella enterica serovar Typhimurium (S. typhimurium).
Methods: We investigated the effects of IFN-g on iron homeostasis and immune function in RAW264.7 macrophages in response to infection with Salmonella typhimurium.
Results: In S. typhimurium-infected phagocytes, IFN-g caused a significant reduction of iron uptake via transferrin receptor 1. In parallel, we observed an enhanced efflux of iron from Salmonella-infected macrophages upon activation with IFN-g, which could be traced back to 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-g exerting a super-inducing effect. This observed regulatory impact of IFN-g reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed S. typhimurium while concomitantly promoting NO and TNF-a production.
Conclusion: Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-g concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. We therefore propose that these regulations reported herein reflect novel antibacterial effects of IFN-g being consistent with the principles of nutritional immunity.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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