Hepcidin and Host Defense against Infectious Diseases

1. Hentze MW, Muckenthaler MU, Andrews NC. Balancing Acts: Molecular Control of Mammalian Iron Metabolism. Cell. 2004;117(3):285–97. 15109490

2. Ratledge C, Dover LG. Iron metabolism in pathogenic bacteria. Annual reviews in microbiology. 2000;54(1):881–941.

3. Skaar EP. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS pathogens. 2013;6(8):e1000949.

4. Nicolas Gl, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proceedings of the National Academy of Sciences. 2001;98(15):8780–5.

5. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. Journal of biological chemistry. 2001;276(11):7806–10. 11113131

6. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. Journal of biological chemistry. 2001;276(11):7811–9. 11113132

7. Krause A, Neitz S, Mägert H-J, Schulz A, Forssmann W-G, Schulz-Knappe P, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Letters. 2000;480(2):147–50.

8. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101(7):2461–3. 12433676

9. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–3. 15514116

10. Nicolas Gl, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proceedings of the National Academy of Sciences. 2002;99(7):4596–601.

11. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. The Journal of Clinical Investigation. 2002;110(7):1037–44. 12370282

12. Kautz Lo, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nature genetics. 2014. doi: 10.1038/ng.2996 24880340

13. Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nature genetics. 2006;38(5):531–9. 16604073

14. Casanovas G, Mleczko-Sanecka K, Altamura S, Hentze MW, Muckenthaler MU. Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD. Journal of molecular medicine. 2009;87(5):471–80. doi: 10.1007/s00109-009-0447-2 19229506

15. Andriopoulos B Jr, Corradini E, Xia Y, Faasse SA, Chen S, Grgurevic L, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nature genetics. 2009;41(4):482–7. doi: 10.1038/ng.335 19252486

16. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. Journal of Clinical Investigation. 2004;113(9):1271–6. 15124018

17. Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood. 2006;108(9):3204–9. 16835372

18. Mayeur C, Leyton PA, Kolodziej SA, Yu B, Bloch KD. BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism. Blood. 2014;124(13):2116–23. doi: 10.1182/blood-2014-04-572644 25075125

19. Rodriguez R, Jung C-L, Gabayan V, Deng JC, Ganz T, Nemeth E, et al. Hepcidin induction by pathogens and pathogen-derived molecules is strongly dependent on interleukin-6. Infection and Immunity. 2014;82(2):745–52. doi: 10.1128/IAI.00983-13 24478088

20. Leal SM Jr, Roy S, Vareechon C, deJesus Carrion S, Clark H, Lopez-Berges MS, et al. Targeting iron acquisition blocks infection with the fungal pathogens Aspergillus fumigatus and Fusarium oxysporum. PLoS pathogens. 2013;9(7):e1003436. doi: 10.1371/journal.ppat.1003436 23853581

21. Lee P, Peng H, Gelbart T, Beutler E. The IL-6-and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and β2-microglobulin-deficient hepatocytes. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(25):9263–5. 15192150

22. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005;106(5):1864–6. 15886319

23. Kim A, Fung E, Parikh SG, Valore EV, Gabayan V, Nemeth E, et al. A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin2014. 1129–36 p.

24. Peyssonnaux C, Zinkernagel AS, Datta V, Lauth X, Johnson RS, Nizet V. TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood. 2006;107(9):3727–32. doi: 10.1182/blood-2005-06-2259 16391018

25. Ripley DA, Morris RH, Maddocks SE. Dual stimulation with bacterial and viral components increases the expression of hepcidin in human monocytes. FEMS microbiology letters. 2014;359(2):161–5. doi: 10.1111/1574-6968.12553 25145495

26. Armitage AE, Eddowes LA, Gileadi U, Cole S, Spottiswoode N, Selvakumar TA, et al. Hepcidin regulations by innate immune and infectious stimuli. Blood. 2011;118(15):4129–39. doi: 10.1182/blood-2011-04-351957 21873546

27. Nguyen N-B, Callaghan KD, Ghio AJ, Haile DJ, Yang F. Hepcidin expression and iron transport in alveolar macrophages. American Journal of Physiology—Lung Cellular and Molecular Physiology. 2006;291(3):L417–L25. 16648237

28. Layoun A, Santos MM. Bacterial cell wall constituents induce hepcidin expression in macrophages through MyD88 signaling. Inflammation. 2012;35(4):1500–6. doi: 10.1007/s10753-012-9463-4 22544439

29. Wu X, Yung L-M, Cheng W-H, Paul BY, Babitt JL, Lin HY, et al. Hepcidin regulation by BMP signaling in macrophages is lipopolysaccharide dependent. PloS one. 2012;7(9):e44622. doi: 10.1371/journal.pone.0044622 23028567

30. Zumerle S, Mathieu JRR, Delga Sp, Heinis Mn, Viatte L, Vaulont S, et al. Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype. Blood. 2014;123(23):3646–50. doi: 10.1182/blood-2014-01-550467 24646470

31. Zhang X, Rovin BH. Beyond anemia: hepcidin, monocytes and inflammation. Biological Chemistry. 2013;394(2):231–8. doi: 10.1515/hsz-2012-0217 23314535

32. Sow FB, Florence WC, Satoskar AR, Schlesinger LS, Zwilling BS, Lafuse WP. Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis. Journal of Leukocyte Biology. 2007;82(4):934–45. 17609338

33. Rochette J, Pointon JJ, Fisher CA, Perera G, Arambepola M, Arichchi DSK, et al. Multicentric origin of hemochromatosis gene (HFE) mutations. The American Journal of Human Genetics. 1999;64(4):1056–62. 10090890

34. Distante S, Robson KJH, Graham-Campbell J, Arnaiz-Villena A, Brissot P, Worwood M. The origin and spread of the HFE-C282Y haemochromatosis mutation. Human genetics. 2004;115(4):269–79. 15290237

35. Hanson EH, Imperatore G, Burke W. HFE gene and hereditary hemochromatosis: a HuGE review. American Journal of Epidemiology. 2001;154(3):193–206. 11479183

36. Weinberg ED. Survival advantage of the hemochromatosis C282Y mutation. Perspectives in biology and medicine. 2008;51(1):98–102.

37. Olsson KS, Ritter B, Hansson N, Chowdhury RR. HLA haplotype map of river valley populations with hemochromatosis traced through five centuries in Central Sweden. European journal of haematology. 2008;81(1):36–46. doi: 10.1111/j.1600-0609.2008.01078.x 18363869

38. Moalem S, Percy ME, Kruck TPA, Gelbart RR. Epidemic pathogenic selection: an explanation for hereditary hemochromatosis? Medical Hypotheses. 2002;59(3):325–9. 12208162

39. Chlosta S, Fishman DS, Harrington L, Johnson EE, Knutson MD, Wessling-Resnick M, et al. The Iron Efflux Protein Ferroportin Regulates the Intracellular Growth of Salmonella enterica. Infection and Immunity. 2006;74(5):3065–7. 16622252

40. Nairz M, Theurl I, Schroll A, Theurl M, Fritsche G, Lindner E, et al. Absence of functional Hfe protects mice from invasive Salmonella enterica Serovar Typhimurium infection via induction of lipocalin-2. Blood. 2009;114:3642–51. doi: 10.1182/blood-2009-05-223354 19700664

41. Kim D-K, Jeong J-H, Lee J-M, Kim KS, Park S-H, Kim YD, et al. Inverse agonist of estrogen-related receptor [gamma] controls Salmonella typhimurium infection by modulating host iron homeostasis. Nat Med. 2014;20(4):419–24. doi: 10.1038/nm.3483 24658075

42. Yuki KE, Eva MM, Richer E, Chung D, Paquet Mn, Cellier M, et al. Suppression of Hepcidin Expression and Iron Overload Mediate Salmonella Susceptibility in Ankyrin 1 ENU-Induced Mutant. PloS one. 2013;8(2):e55331. doi: 10.1371/journal.pone.0055331 23390527

43. Wang L, Johnson EE, Shi HN, Walker WA, Wessling-Resnick M, Cherayil BJ. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. The Journal of Immunology. 2008;181(4):2723–31. 18684963

44. Wallace DF, McDonald CJ, Ostini L, Subramaniam VN. Blunted hepcidin response to inflammation in the absence of Hfe and transferrin receptor 2. Blood. 2011;117(10):2960–6. doi: 10.1182/blood-2010-08-303859 21245482

45. Frazer DM, Wilkins SJ, Millard KN, McKie AT, Vulpe CD, Anderson GJ. Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE. British Journal of Haematology. 2004;126(3):434–6. 15257718

46. Constante M, Jiang W, Wang D, Raymond V-A, Bilodeau M, Santos MM. Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006;291(2):G229–G37. 16565419

47. Gordeuk VR, McLaren CE, MacPhail AP, Deichsel G, Bothwell TH. Associations of iron overload in Africa with hepatocellular carcinoma and tuberculosis: Strachan's 1929 thesis revisited. Blood. 1996;87(8):3470–6. 8605366

48. Boelaert JR, Vandecasteele SJ, Appelberg R, Gordeuk VR. The effect of the host's iron status on tuberculosis. Journal of Infectious Diseases. 2007;195(12):1745–53. 17492589

49. Olakanmi O, Schlesinger LS, Britigan BE. Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis within human macrophages. Journal of Leukocyte Biology. 2007;81(1):195–204. 17038583

50. Olakanmi O, Schlesinger LS, Ahmed A, Britigan BE. Intraphagosomal Mycobacterium tuberculosis Acquires Iron from Both Extracellular Transferrin and Intracellular Iron Pools: IMPACT OF INTERFERON-γ AND HEMOCHROMATOSIS. Journal of Biological Chemistry. 2002;277(51):49727–34. 12399453

51. Gomes-Pereira S, Rodrigues PN, Appelberg R, Gomes MS. Increased Susceptibility to Mycobacterium avium in Hemochromatosis Protein HFE-Deficient Mice. Infection and Immunity. 2008;76(10):4713–9. doi: 10.1128/IAI.00612-08 18694968

52. Johnson EE, Sandgren A, Cherayil BJ, Murray M, Wessling-Resnick M. Role of Ferroportin in Macrophage-Mediated Immunity. Infection and Immunity. 2010;78(12):5099–106. doi: 10.1128/IAI.00498-10 20837712

53. Van Zandt KE, Sow FB, Florence WC, Zwilling BS, Satoskar AR, Schlesinger LS, et al. The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome. Journal of Leukocyte Biology. 2008;84(3):689–700. doi: 10.1189/jlb.1107781 18586980

54. Ben-Othman R, Flannery AR, Miguel DC, Ward DM, Kaplan J, Andrews NW. Leishmania-Mediated Inhibition of Iron Export Promotes Parasite Replication in Macrophages. PLoS Pathog. 2014;10(1):e1003901. doi: 10.1371/journal.ppat.1003901 24497831

55. Paradkar PN, De Domenico I, Durchfort N, Zohn I, Kaplan J, Ward DM. Iron depletion limits intracellular bacterial growth in macrophages. Blood. 2008;112(3):866–74. doi: 10.1182/blood-2007-12-126854 18369153

56. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. International Journal of Infectious Diseases. 2007;11(6):482–7. 17600748

57. Weinberg ED. Iron availability and infection. Biochimica et Biophysica Acta (BBA)-General Subjects. 2009;1790(7):600–5.

58. Walker EM, Walker SM. Effects of iron overload on the immune system. Annals of Clinical & Laboratory Science. 2000;30(4):354–65.

59. Arezes Jo, Jung G, Gabayan V, Valore E, Ruchala P, Gulig PA, et al. Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism against the Siderophilic Bacterium Vibrio vulnificus. Cell host & microbe. 2015;17(1):47–57.

60. Van Eijk LT, Kroot JJ, Tromp M, van der Hoeven JG, Swinkels DW, Pickkers P. Inflammation-induced hepcidin-25 is associated with the development of anemia in septic patients: an observational study. Critical Care. 2011;15(1):R9. doi: 10.1186/cc9408 21219610

61. De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, et al. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. The Journal of Clinical Investigation. 2010;120(7):2395–405. doi: 10.1172/JCI42011 20530874

62. Huang Y-H, Yang Y-L, Tiao M-M, Kuo H-C, Huang L-T, Chuang J-H. Hepcidin protects against lipopolysaccharide-induced liver injury in a mouse model of obstructive jaundice. Peptides. 2012;35(2):212–7. doi: 10.1016/j.peptides.2012.03.032 22504010

63. Zeng C, Chen Q, Zhang K, Chen Q, Song S, Fang X. Hepatic Hepcidin Protects against Polymicrobial Sepsis in Mice by Regulating Host Iron Status. Anesthesiology. 2014;122(2):374–86.

64. Chen Q, Song S, Chen Q, Zeng C, Zheng X, Wang J, et al. Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury. Critical Care. 2014;18(4):470. doi: 10.1186/s13054-014-0470-8 25096529

65. Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. The Lancet. 2006;367(9505):133–43. S0140-6736(06)67962-2.

66. Smith AW, Hendrickse RG, Harrison C, Hayes RJ, Greenwood BM. The effects on malaria of treatment of iron-deficiency anaemia with oral iron in Gambian children. Annals of tropical paediatrics. 1989;9(1):17–23. 2471438

67. Oppenheimer SJ, Gibson FD, Macfarlane SB, Moody JB, Harrison C, Spencer A, et al. Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1986;80(4):603–12. 3101243

68. Mebrahtu T, Stoltzfus RJ, Chwaya HM, Jape JK, Savioli L, Montresor A, et al. Low-dose daily iron supplementation for 12 months does not increase the prevalence of malarial infection or density of parasites in young Zanzibari children. The Journal of nutrition. 2004;134(11):3037–41. 15514272

69. Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte JJ, Font F, et al. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. The Lancet. 1997;350(9081):844–50.

70. Gwamaka M, Kurtis JD, Sorensen BE, Holte S, Morrison R, Mutabingwa TK, et al. Iron Deficiency Protects Against Severe Plasmodium falciparum Malaria and Death in Young Children. Clinical Infectious Diseases. 2012;54(8):1137–44. doi: 10.1093/cid/cis010 22354919

71. Kabyemela ER, Fried M, Kurtis JD, Mutabingwa TK, Duffy PE. Decreased susceptibility to Plasmodium falciparum infection in pregnant women with iron deficiency. Journal of Infectious Diseases. 2008;198(2):163–6. doi: 10.1086/589512 18500927

72. Nyakeriga AM, Troye-Blomberg M, Dorfman JR, Alexander ND, Bäck R, Kortok M, et al. Iron deficiency and malaria among children living on the coast of Kenya. Journal of Infectious Diseases. 2004;190(3):439–44. 15243915

73. Koka S, Fοller M, Lamprecht G, Boini KM, Lang C, Huber SM, et al. Iron deficiency influences the course of malaria in Plasmodium berghei infected mice. Biochemical and Biophysical Research Communications. 2007;357(3):608–14. 17445762

74. Matsuzaki-Moriya C, Tu L, Ishida H, Imai T, Suzue K, Hirai M, et al. A critical role for phagocytosis in resistance to malaria in iron-deficient mice. European Journal of Immunology. 2011;41(5):1365–75. doi: 10.1002/eji.201040942 21469097

75. Casals-Pascual C, Huang H, Lakhal-Littleton S, Thezenas ML, Kai O, Newton CRJC, et al. Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria. haematologica. 2012;97(11):1695–8. doi: 10.3324/haematol.2012.065854 22689680

76. de Mast Q, Nadjm B, Reyburn H, Kemna EHJM, Amos B, Laarakkers CMM, et al. Assessment of Urinary Concentrations of Hepcidin Provides Novel Insight into Disturbances in Iron Homeostasis during Malarial Infection. Journal of Infectious Diseases. 2009;199(2):253–62. doi: 10.1086/595790 19032104

77. Portugal S, Carret C, Recker M, Armitage AE, Gonçalves LA, Epiphanio S, et al. Host mediated regulation of superinfection in malaria. Nature medicine. 2011;17(6):732–7. doi: 10.1038/nm.2368 21572427

78. Wang H-Z, He Y-X, Yang C-J, Zhou W, Zou C-G. Hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection. The Journal of Immunology. 2011;187(12):6410–6. doi: 10.4049/jimmunol.1101436 22084434

79. Armitage AE, Pinches R, Eddowes LA, Newbold CI, Drakesmith H. Plasmodium falciparum infected erythrocytes induce hepcidin (HAMP) mRNA synthesis by peripheral blood mononuclear cells. British Journal of Haematology. 2009;147(5):769–71. doi: 10.1111/j.1365-2141.2009.07880.x 19747361

80. Huang H, Lamikanra AA, Alkaitis MS, Thézénas ML, Ramaprasad A, Moussa E, et al. Interleukin-10 Regulates Hepcidin in Plasmodium falciparum Malaria. PloS one. 2014;9(2):e88408. doi: 10.1371/journal.pone.0088408 24520384

81. Spottiswoode N, Duffy PE, Drakesmith H. Iron, anemia and hepcidin in malaria. Frontiers in Pharmacology. 2014;5. doi: 10.3389/fphar.2014.00125 24910614

82. Wang X-h, Cheng P-P, Jiang F, Jiao X-Y. The Effect of Hepatitis B Virus Infection on Hepcidin Expression in Hepatitis B Patients. Annals of Clinical & Laboratory Science. 2013;43(2):126–34.

83. Armitage AE, Stacey AR, Giannoulatou E, Marshall E, Sturges P, Chatha K, et al. Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections. Proceedings of the National Academy of Sciences. 2014;111(33):12187–92.

84. Lambrecht RW, Sterling RK, Naishadham D, Stoddard AM, Rogers T, Morishima C, et al. Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C. Gastroenterology. 2011;140(5):1490–500. e3. doi: 10.1053/j.gastro.2011.01.053 21335007

85. Tung BY, Emond MJ, Bronner MP, Raaka SD, Cotler SJ, Kowdley KV. Hepatitis C, iron status, and disease severity: relationship with HFE mutations. Gastroenterology. 2003;124(2):318–26. 12557137

86. Lal P, Fernandes H, Koneru B, Albanese E, Hameed M. C282Y mutation and hepatic iron status in hepatitis C and cryptogenic cirrhosis. Archives of pathology & laboratory medicine. 2000;124(11):1632–5.

87. Fujita N, Sugimoto R, Takeo M, Urawa N, Mifuji R, Tanaka H, et al. Hepcidin Expression in the Liver: Relatively Low Level in Patients with Chronic Hepatitis C. Molecular Medicine. 2007;13(1–2):97–104. 17515961

88. Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL. Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. Journal of clinical gastroenterology. 2005;39(1):71–4. 15599216

89. Girelli D, Pasino M, Goodnough JB, Nemeth E, Guido M, Castagna A, et al. Reduced serum hepcidin levels in patients with chronic hepatitis C. Journal of hepatology. 2009;51(5):845–52. doi: 10.1016/j.jhep.2009.06.027 19729219

90. Moriya K, Miyoshi H, Shinzawa S, Tsutsumi T, Fujie H, Goto K, et al. Hepatitis C virus core protein compromises iron-induced activation of antioxidants in mice and HepG2 cells. Journal of Medical Virology. 2010;82(5):776–92. doi: 10.1002/jmv.21661 20336713

91. Miura K, Taura K, Kodama Y, Schnabl B, Brenner DA. Hepatitis C virus–induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity. Hepatology. 2008;48(5):1420–9. doi: 10.1002/hep.22486 18671304

92. Nishina S, Hino K, Korenaga M, Vecchi C, Pietrangelo A, Mizukami Y, et al. Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology. 2008;134(1):226–38. doi: 10.1053/j.gastro.2007.10.011 18166355

93. Ross SL, Tran L, Winters A, Lee K-J, Plewa C, Foltz I, et al. Molecular mechanism of hepcidin-mediated ferroportin internalization requires ferroportin lysines, not tyrosines or JAK-STAT. Cell Metabolism. 2012;15(6):905–17. doi: 10.1016/j.cmet.2012.03.017 22682226

94. Pagani A, Nai A, Corna G, Bosurgi L, Rovere-Querini P, Camaschella C, et al. Low hepcidin accounts for the proinflammatory status associated with iron deficiency. Blood. 2011;118(3):736–46. doi: 10.1182/blood-2011-02-337212 21628413

95. Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science. 2008;320(5879):1088–92. doi: 10.1126/science.1157121 18451267

96. Riba M, Rausa M, Sorosina M, Cittaro D, Manteiga JMG, Nai A, et al. A Strong Anti-Inflammatory Signature Revealed by Liver Transcription Profiling of Tmprss6-/- Mice. PloS one. 2013;8(7):e69694. doi: 10.1371/journal.pone.0069694 23922777

97. Hunter HN, Fulton DB, Ganz T, Vogel HJ. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. Journal of Biological Chemistry. 2002;277(40):37597–603. 12138110

98. Maisetta G, Petruzzelli R, Brancatisano FL, Esin S, Vitali A, Campa M, et al. Antimicrobial activity of human hepcidin 20 and 25 against clinically relevant bacterial strains: effect of copper and acidic pH. Peptides. 2010;31(11):1995–2002. doi: 10.1016/j.peptides.2010.08.007 20713108

99. Potrykus J, Stead D, MacCallum DM, Urgast DS, Raab A, van Rooijen N, et al. Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events. PLoS pathogens. 2013;9(10):e1003676. doi: 10.1371/journal.ppat.1003676 24146619

100. D'Alessio F, Hentze MW, Muckenthaler MU. The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. Journal of hepatology. 2012;57(5):1052–60. doi: 10.1016/j.jhep.2012.06.015 22728873