Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events

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Nutritional immunity – the withholding of nutrients by the host – has long been recognised as an important factor that shapes bacterial-host interactions. However, the dynamics of nutrient availability within local host niches during fungal infection are poorly defined. We have combined laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS), MALDI imaging and immunohistochemistry with microtranscriptomics to examine iron homeostasis in the host and pathogen in the murine model of systemic candidiasis. Dramatic changes in the renal iron landscape occur during disease progression. The infection perturbs global iron homeostasis in the host leading to iron accumulation in the renal medulla. Paradoxically, this is accompanied by nutritional immunity in the renal cortex as iron exclusion zones emerge locally around fungal lesions. These exclusion zones correlate with immune infiltrates and haem oxygenase 1-expressing host cells. This local nutritional immunity decreases iron availability, leading to a switch in iron acquisition mechanisms within mature fungal lesions, as revealed by laser capture microdissection and qRT-PCR analyses. Therefore, a complex interplay of systemic and local events influences iron homeostasis and pathogen-host dynamics during disease progression.

Vyšlo v časopise: Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events. PLoS Pathog 9(10): e32767. doi:10.1371/journal.ppat.1003676
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003676

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Zdroje

1. HaasH, EisendleM, TurgeonBG (2008) Siderophores in fungal physiology and virulence. Annu Rev Phytopathol 46: 149–187.

2. OgawaM (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81: 2844–2853.

3. WangH, NishiyaK, ItoH, HosokawaT, HashimotoK, et al. (2001) Iron deposition in renal biopsy specimens from patients with kidney diseases. Am J Kidney Dis 38: 1038–1044.

4. DrakesmithH, PrenticeAM (2012) Hepcidin and the iron-infection axis. Science 338: 768–772.

5. Latunde-DadaGO (2009) Iron metabolism: microbes, mouse, and man. Bioessays 31: 1309–1317.

6. WeinbergED (2009) Iron availability and infection. Biochim Biophys Acta 1790: 600–605.

7. CorbinBD, SeeleyEH, RaabA, FeldmannJ, MillerMR, et al. (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319: 962–965.

8. HoodMI, SkaarEP (2012) Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 10: 525–537.

9. JohnsonEE, Wessling-ResnickM (2012) Iron metabolism and the innate immune response to infection. Microbes Infect 14: 207–216.

10. WardRJ, CrichtonRR, TaylorDL, Della CorteL, SraiSK, et al. (2011) Iron and the immune system. J Neural Transm 118: 315–28.

11. BarryDM, ReeveAW (1988) Iron and infection. Br Med J (Clin Res Ed) 296: 1736.

12. FeldmanHI, SantannaJ, GuoW, FurstH, FranklinE, et al. (2002) Iron administration and clinical outcomes in hemodialysis patients. J Am SocNephrol 13: 734–744.

13. BrownGD, DenningDW, GowNA, LevitzSM, NeteaMG, et al. (2012) Hidden killers: human fungal infections. Sci Transl Med 4: 165rv13.

14. AlmeidaRS, WilsonD, HubeB (2009) Candida albicans iron acquisition within the host. FEMS Yeast Res 9: 1000–1012.

15. JungWH, HuG,KuoW, KronstadJW (2009) Role of ferroxidases in iron uptake and virulence of Cryptococcus neoformans. Eukaryot Cell 8: 1511–1520.

16. IbrahimAS, SpellbergB, EdwardsJJr (2008) Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis 21: 620–5.

17. MencacciA, CenciE, BoelaertJR, BucciP, MosciP, et al. (1997) Iron overload alters innate and T helper cell responses to Candida albicans in mice. J Infect Dis 175: 1467–76.

18. ArmitageAE, EddowesLA, GileadiU, ColeS, SpottiswoodeN, et al. (2011) Hepcidin regulation by innate immune and infectious stimuli. Blood 118: 4129–4139.

19. SardiJC, ScorzoniL, BernardiT, Fusco-AlmeidaAM, Mendes GianniniMJ (2013) Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol 62: 10–24.

20. EneIV, HeilmannCJ, SorgoAG, WalkerLA, de KosterCG, et al. (2012) Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans. Proteomics 12: 3164–3179.

21. KaloritiD, TillmannA, CookE, JacobsenM, YouT, et al. (2012) Combinatorial stresses kill pathogenic Candida species. Med Mycol 50: 699–709.

22. LorenzMC, FinkGR (2001) The glyoxylate cycle is required for fungal virulence. Nature 412: 83–86.

23. RoemerT, JiangB, DavisonJ, KetelaT, VeilletteK, et al. (2003) Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol 50: 167–181.

24. RamananN, WangY (2000) A high-affinity iron permease essential for Candida albicans virulence. Science 288: 1062–1064.

25. NavarathnaDH, RobertsDD (2010) Candida albicans heme oxygenase and its product CO contribute to pathogenesis of candidemia and alter systemic chemokine and cytokine expression. Free Radic Biol Med 49: 1561–1573.

26. GowNA, van de VeerdonkFL, BrownAJP, NeteaMG (2011) Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol 10: 112–122.

27. MacCallumDM, OddsFC (2005) Temporal events in the intravenous challenge model for experimental Candida albicans infections in female mice. Mycoses 48: 151–161.

28. FonziW, IrwinM (1993) Isogenic strain construction and gene mapping in Candida albicans. Genetics 134: 717–128.

29. MatuschA, FennLS, DepboyluC, KlietzM, StrohmerS, et al. (2012) Combined elemental and biomolecular mass spectrometry imaging for probing the inventory of tissue at a micrometer scale. Anal Chem 84: 3170–3178.

30. MacCallumDM, CastilloL, NatherK, MunroCA, BrownAJP, et al. (2009) Property differences among the four major Candida albicans strain clades. Eukaryot Cell 8: 373–387.

31. SuckauD, ResemannA, SchuerenbergM, HufnagelP, FranzenJ, et al. (2003) A novel MALDI LIFT-TOF/TOF mass spectrometer for proteomics. Anal Bioanal Chem 376: 952–965.

32. SeeleyEH, SchwambornK, CaprioliRM (2011) Imaging of intact tissue sections: moving beyond the microscope. J Biol Chem 286: 25459–25466.

33. ShimmaS, SetouM (2007) Mass microscopy to reveal distinct localization of heme B (m/z 616) in colon cancer liver metastasis. J Mass Spectrom Soc Jpn 55: 145–148.

34. SpellbergB, IbrahimAS, EdwardsJEJr, FillerSG (2005) Mice with disseminated candidiasis die of progressive sepsis. J Infect Dis 192: 336–343.

35. ThomsonAM, RogersJT, LeedmanPJ (1999) Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation. Int J Biochem Cell Biol 31: 1139–1152.

36. El HageChahineJM, HémadiM, Ha-DuongNT (2012) Uptake and release of metal ions by transferrin and interaction with receptor 1. Biochim Biophys Acta 1820: 334–347.

37. HainesDD, LekliI, TeissierP, BakI, TosakiIA (2012) Role of haem oxygenase-1 in resolution of oxidative stress-related pathologies: focus on cardiovascular, lung, neurological and kidney disorders. ActaPhysiol (Oxf) 204: 487–501.

38. MainesMD (1988) Hemeoxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2: 2557–2568.

39. KovtunovychG, EckhausMA, GhoshMC, Ollivierre-WilsonH, RouaultTA (2010) Dysfunction of the heme recycling system in hemeoxygenase 1-deficient mice: effects on macrophage viability and tissue iron distribution. Blood 116: 6054–6062.

40. LloydCM, PhillipsAR, CooperGJ, DunbarPR (2008) Three-colour fluorescence immunohistochemistry reveals the diversity of cells staining for macrophage markers in murine spleen and liver. J Immunol Methods 334: 70–81.

41. Van RooijenN, Van NieuwmegenR (1984) Elimination of phagocytic cells in the spleen after intravenous injection of liposome encapsulated dichloromethylene-diphosphonate. An enzyme-histochemical study. Cell Tissue Res 238: 355–358.

42. HeymannP, GeradsM, SchallerM, DromerF, WinkelmannG, et al. (2002) Thesiderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun 70: 5246–5255.

43. KnightSA, VilaireG, LesuisseE (2005) DancisA (2005) Iron acquisition from transferrin by Candida albicans depends on the reductive pathway. InfectImmun 73: 5482–5492.

44. SantosR, BuissonN, KnightS, DancisA, CamadroJM, et al. (2003) Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haemoxygenase. Microbiology 149: 579–588.

45. ParkCH, ValoreEV, WaringAJ, GanzT (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276: 7806–7810.

46. SmithCP, ThevenodF (2009) Iron transport and the kidney. Biochim Biophys Acta 1790: 724–730.

47. QianQ, JutilaMA, Van RooijenN, CutlerJE (1994) Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. J Immunol 152: 5000–5008.

48. PendrakML, ChaoMP, YanSS, RobertsDD (2004) Hemeoxygenase of Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to α-biliverdin. J Biol Chem 279: 3426–3433.

49. McManusJF, CasonJE (1950) Carbohydrate histochemistry studied by acetylation techniques. J Exp Med 91: 651–654.

50. UrgastDS, OuO, GordonMJ, RaabA, NixonGF, et al. (2012) Microanalytical isotope ratio measurements and elemental mapping using laser ablation ICP-MS for tissue thin sections: zinc tracer studies in rats. Anal Bioanal Chem 402: 287–297.

51. Urgast D, Beattie J, Feldman J (2011) Multi-elemental imaging of rodent tissues with LA-ICP-MS [Abstract PC-038]. In: Book of Abstracts of European Winter Conference on Plasma Spectrochemistry; 30 January–4 February 2011; Zaragoza, Spain. EWCPS 2011.

52. MarakalalaMJ, VautierS, PotrykusJ, WalkerLA, ShepardsonKM, et al. (2013) Differential adaptation of Candida albicans in vivo modulates immune recognition by Dectin-1. PLoS Pathogens 9 (4) e1003315 doi: 10.1371/journal.ppat.1003315

53. BarelleCJ, PriestCL, MaccallumDM, GowNA, OddsFC, et al. (2006) Niche-specific regulation of central metabolic pathways in a fungal pathogen. Cell Microbiol 8: 961–71.