Lipocalin-2 ensures host defense against Salmonella Typhimurium by controlling macrophage iron homeostasis and immune response

European Journal of Immunology
Manfred NairzGünter Weiss

Abstract

Lipocalin-2 (Lcn2) is an innate immune peptide with pleiotropic effects. Lcn2 binds iron-laden bacterial siderophores, chemo-attracts neutrophils and has immunomodulatory and apoptosis-regulating effects. In this study, we show that upon infection with Salmonella enterica serovar Typhimurium, Lcn2 promotes iron export from Salmonella-infected macrophages, which reduces cellular iron content and enhances the generation of pro-inflammatory cytokines. Lcn2 represses IL-10 production while augmenting Nos2, TNF-α, and IL-6 expression. Lcn2(-/-) macrophages have elevated IL-10 levels as a consequence of increased iron content. The crucial role of Lcn-2/IL-10 interactions was further demonstrated by the greater ability of Lcn2(-/-) IL-10(-/-) macrophages and mice to control intracellular Salmonella proliferation in comparison to Lcn2(-/-) counterparts. Overexpression of the iron exporter ferroportin-1 in Lcn2(-/-) macrophages represses IL-10 and restores TNF-α and IL-6 production to the levels found in wild-type macrophages, so that killing and clearance of intracellular Salmonella is promoted. Our observations suggest that Lcn2 promotes host resistance to Salmonella Typhimurium infection by binding bacterial siderophores and suppress...Continue Reading

References

Oct 29, 2000·British Journal of Haematology·A ScaccabarozziS Fargion
Mar 12, 2002·European Journal of Clinical Investigation·Günter Weiss
Jan 11, 2003·Blood·Susanne LudwiczekGünter Weiss
Jan 16, 2003·Immunology Letters·Helen L Collins
Mar 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·K HantkeG Winkelmann
Apr 28, 2004·Cell·Matthias W HentzeNancy C Andrews
Jun 3, 2004·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Susanne LudwiczekGuenter Weiss
Nov 20, 2004·Nature Reviews. Microbiology·Ulrich E Schaible, Stefan H E Kaufmann
Mar 2, 2005·Best Practice & Research. Clinical Haematology·Günter Weiss
Mar 11, 2005·The New England Journal of Medicine·Guenter Weiss, Lawrence T Goodnough
Dec 27, 2005·Cell·Laxminarayana R DevireddyMichael R Green
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thorsten BergerTak W Mak
May 24, 2006·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Niels Borregaard, Jack B Cowland
Oct 4, 2006·Annual Review of Physiology·Nancy C Andrews, Paul J Schmidt
Apr 11, 2007·Infection and Immunity·Aaron L NelsonJeffrey N Weiser
Jun 4, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Milan TheurlGuenter Weiss
Aug 5, 2008·Biochimica Et Biophysica Acta·Eugene D Weinberg
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hiroyuki SaigaKiyoshi Takeda
Jun 29, 2010·Nature Chemical Biology·Guanhu BaoJonathan Barasch
Oct 23, 2010·Cellular Microbiology·Manfred NairzGünter Weiss
Apr 26, 2011·Trends in Immunology·Gaetano CairoMassimo Locati
Mar 24, 2012·Journal of Innate Immunity·Tomas Ganz
Apr 20, 2012·Biochimica Et Biophysica Acta·Subhankar ChakrabortySurinder K Batra
Jul 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gayathri SrinivasanMatam Vijay-Kumar
Sep 12, 2012·European Journal of Immunology·Andrea SchrollGuenter Weiss
Nov 10, 2012·Science·Hal Drakesmith, Andrew M Prentice
Nov 28, 2012·PloS One·Lokesh GuglaniShabaana A Khader

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Citations

Mar 13, 2016·Medical Hypotheses·Yanfang XiaChristian Lehmann
Feb 6, 2018·Oncoimmunology·Christina MertensMichaela Jung
May 1, 2020·Journal of Cellular Physiology·Seyed Mahdi Hosseiniyan KhatibiSepideh Zununi Vahed
Apr 27, 2017·Frontiers in Cellular and Infection Microbiology·Manfred NairzGünter Weiss
Jul 9, 2020·Immunology·Ana Sousa GerósJoe N Frost
Jun 20, 2017·Annual Review of Nutrition·Xia XiaoMatam Vijay-Kumar
Jan 7, 2020·Cellular and Molecular Life Sciences : CMLS·Sayan GhoshDebasish Sinha
Aug 4, 2019·Critical Care : the Official Journal of the Critical Care Forum·Fanglin LuHiroshi Morisaki
Oct 28, 2017·Frontiers in Microbiology·Christopher J Anderson, Melissa M Kendall
Oct 24, 2020·Expert Review of Anti-infective Therapy·Lara Valente de SouzaGünter Weiss
Jun 3, 2020·The Journal of Allergy and Clinical Immunology·Franziska Roth-WalterErika Jensen-Jarolim
Jun 10, 2021·Klinicheskaia laboratornaia diagnostika·Ekaterina Dmitrievna LyutsovaY D Bocheva
Jun 24, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Shengxian Li, Yong Huang
Jul 13, 2021·MicroLife·Olivier Cunrath, Jacob D Palmer
Jul 30, 2021·Ageing Research Reviews·Doortje W DekensPetrus J W Naudé
Sep 29, 2017·Journal of the American Chemical Society·Timothy C Johnstone, Elizabeth M Nolan

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