Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content

Advertisement

Springer Nature Link
Log in

Thriving within the host: Candida spp. interactions with phagocytic cells

  • Review
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Certain Candida spp. (e.g. C. albicans, C. tropicalis, C. parapsilosis and C. glabrata) are not only well-adapted fungal commensals of humans, but are also able to cause superficial mucosal infections or even systemic disease. Professional phagocytes (neutrophils, macrophages and dendritic cells) constitute the first line of defence against Candida spp. Here, we review the interactions of phagocytes with pathogenic Candida spp., focusing on macrophages and neutrophils. We discuss the mechanisms involved in recognition, uptake and killing of these fungi. We go on to analyse the cellular responses of these yeasts towards phagocyte-imposed stresses, including metabolic flexibility, robust oxidative stress response and ability to cope with nitrosative stress. Finally, we address strategies that allow these opportunistic pathogens to thrive within the host, evading and escaping from the phagocyte attack.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S et al (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657–662

    Article  PubMed  CAS  Google Scholar 

  2. Mavor AL, Thewes S, Hube B (2005) Systemic fungal infections caused by Candida species: epidemiology, infection process and virulence attributes. Curr Drug Targets 6:863–874

    Article  PubMed  CAS  Google Scholar 

  3. Hube B (2009) Fungal adaptation to the host environment. Curr Opin Microbiol 12:347–349

    Article  PubMed  Google Scholar 

  4. Mochon AB, Ye J, Kayala MA, Wingard JR, Clancy CJ et al (2010) Serological profiling of a Candida albicans protein microarray reveals permanent host-pathogen interplay and stage-specific responses during candidemia. PLoS Pathog 6:e1000827

    Article  PubMed  CAS  Google Scholar 

  5. Rosenbach A, Dignard D, Pierce JV, Whiteway M, Kumamoto CA (2010) Adaptations of Candida albicans for growth in the mammalian intestinal tract. Eukaryot Cell 9:1075–1086

    Article  PubMed  CAS  Google Scholar 

  6. Moyes DL, Naglik JR (2011) Mucosal immunity and Candida albicans infection. Clin Dev Immunol 2011:346307

    Article  PubMed  CAS  Google Scholar 

  7. Perlroth J, Choi B, Spellberg B (2007) Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol 45:321–346

    Article  PubMed  Google Scholar 

  8. Moran G, Coleman D, Sullivan D (2012) An Introduction to the Medically Important Candida species. In: Calderone RA, Clancy CJ (eds) Candida and candidiasis, 2nd edn. ASM Press, Washington, DC

    Google Scholar 

  9. Koh AY, Kohler JR, Coggshall KT, Van Rooijen N, Pier GB (2008) Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog 4:e35

    Article  PubMed  CAS  Google Scholar 

  10. Pasqualotto AC, Nedel WL, Machado TS, Severo LC (2006) Risk factors and outcome for nosocomial breakthrough candidaemia. J Infect 52:216–222

    Article  PubMed  CAS  Google Scholar 

  11. Shoham S, Levitz SM (2005) The immune response to fungal infections. Br J Haematol 129:569–582

    Article  PubMed  Google Scholar 

  12. Sudbery P, Gow N, Berman J (2004) The distinct morphogenic states of Candida albicans. Trends Microbiol 12:317–324

    Article  PubMed  CAS  Google Scholar 

  13. Moran GP, Coleman DC, Sullivan DJ (2012) Candida albicans versus Candida dubliniensis: why is C. albicans more pathogenic? Int J Microbiol 2012:205921

    PubMed  Google Scholar 

  14. Yoshijima Y, Murakami K, Kayama S, Liu D, Hirota K et al (2010) Effect of substrate surface hydrophobicity on the adherence of yeast and hyphal Candida. Mycoses 53:221–226

    Article  PubMed  Google Scholar 

  15. Sundstrom P (2002) Adhesion in Candida spp. Cell Microbiol 4:461–469

    Article  PubMed  CAS  Google Scholar 

  16. Wächtler B, Wilson D, Haedicke K, Dalle F, Hube B (2011) From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLoS ONE 6:e17046

    Article  PubMed  CAS  Google Scholar 

  17. d’Enfert C (2006) Biofilms and their role in the resistance of pathogenic Candida to antifungal agents. Curr Drug Targets 7:465–470

    Article  PubMed  Google Scholar 

  18. Ganguly S, Mitchell AP (2011) Mucosal biofilms of Candida albicans. Curr Opin Microbiol 14:380–385

    Article  PubMed  CAS  Google Scholar 

  19. Taff HT, Nett JE, Zarnowski R, Ross KM, Sanchez H et al (2012) A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog 8:e1002848

    Article  PubMed  CAS  Google Scholar 

  20. Xie Z, Thompson A, Sobue T, Kashleva H, Xu H, et al (2012) Candida albicans biofilms do not trigger reactive oxygen species and evade neutrophil killing. J Infect Dis 206(12):1936–45

    Google Scholar 

  21. Uppuluri P, Chaturvedi AK, Srinivasan A, Banerjee M, Ramasubramaniam AK et al (2010) Dispersion as an important step in the Candida albicans biofilm developmental cycle. PLoS Pathog 6:e1000828

    Article  PubMed  CAS  Google Scholar 

  22. Naglik J, Albrecht A, Bader O, Hube B (2004) Candida albicans proteinases and host/pathogen interactions. Cell Microbiol 6:915–926

    Article  PubMed  CAS  Google Scholar 

  23. Schaller M, Borelli C, Korting HC, Hube B (2005) Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 48:365–377

    Article  PubMed  CAS  Google Scholar 

  24. Stehr F, Felk A, Gacser A, Kretschmar M, Mahnss B et al (2004) Expression analysis of the Candida albicans lipase gene family during experimental infections and in patient samples. FEMS Yeast Res 4:401–408

    Article  PubMed  CAS  Google Scholar 

  25. Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W et al (2006) Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 117:84–92

    Article  PubMed  Google Scholar 

  26. van Asbeck EC, Clemons KV, Stevens DA (2009) Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility. Crit Rev Microbiol 35:283–309

    Article  PubMed  CAS  Google Scholar 

  27. Trofa D, Gacser A, Nosanchuk JD (2008) Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 21:606–625

    Article  PubMed  CAS  Google Scholar 

  28. Kothavade RJ, Kura MM, Valand AG, Panthaki MH (2010) Candida tropicalis: its prevalence, pathogenicity and increasing resistance to fluconazole. J Med Microbiol 59:873–880

    Article  PubMed  CAS  Google Scholar 

  29. Nucci M, Queiroz-Telles F, Tobon AM, Restrepo A, Colombo AL (2010) Epidemiology of opportunistic fungal infections in Latin America. Clin Infect Dis 51:561–570

    Article  PubMed  Google Scholar 

  30. Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S et al (2004) Genome evolution in yeasts. Nature 430:35–44

    Article  PubMed  Google Scholar 

  31. Lee I, Fishman NO, Zaoutis TE, Morales KH, Weiner MG et al (2009) Risk factors for fluconazole-resistant Candida glabrata bloodstream infections. Arch Intern Med 169:379–383

    Article  PubMed  Google Scholar 

  32. Fradin C, De Groot P, MacCallum D, Schaller M, Klis F et al (2005) Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood. Mol Microbiol 56:397–415

    Article  PubMed  CAS  Google Scholar 

  33. van ‘t Wout JW, Linde I, Leijh PC, van Furth R (1988) Contribution of granulocytes and monocytes to resistance against experimental disseminated Candida albicans infection. Eur J Clin Microbiol Infect Dis 7:736–741

    Article  PubMed  Google Scholar 

  34. Svobodova E, Staib P, Losse J, Hennicke F, Barz D et al (2012) Differential interaction of the two related fungal species Candida albicans and Candida dubliniensis with human neutrophils. J Immunol 189:2502–2511

    Article  PubMed  CAS  Google Scholar 

  35. Kowanko IC, Ferrante A, Harvey DP, Carman KL (1991) Granulocyte-macrophage colony-stimulating factor augments neutrophil killing of Torulopsis glabrata and stimulates neutrophil respiratory burst and degranulation. Clin Exp Immunol 83:225–230

    Article  PubMed  CAS  Google Scholar 

  36. Lindemann RA, Franker CK (1991) Phagocyte-mediated killing of Candida tropicalis. Mycopathologia 113:81–87

    Article  PubMed  CAS  Google Scholar 

  37. Linden JR, Maccani MA, Laforce-Nesbitt SS, Bliss JM (2010) High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils. Med Mycol 48:355–364

    Article  PubMed  CAS  Google Scholar 

  38. Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11:762–774

    Article  PubMed  CAS  Google Scholar 

  39. Romagnoli G, Nisini R, Chiani P, Mariotti S, Teloni R et al (2004) The interaction of human dendritic cells with yeast and germ-tube forms of Candida albicans leads to efficient fungal processing, dendritic cell maturation, and acquisition of a Th1 response-promoting function. J Leukoc Biol 75:117–126

    Article  PubMed  CAS  Google Scholar 

  40. Netea MG, Gijzen K, Coolen N, Verschueren I, Figdor C et al (2004) Human dendritic cells are less potent at killing Candida albicans than both monocytes and macrophages. Microbes Infect 6:985–989

    Article  PubMed  CAS  Google Scholar 

  41. Ramirez-Ortiz ZG, Means TK (2012) The role of dendritic cells in the innate recognition of pathogenic fungi (A. fumigatus, C. neoformans and C. albicans). Virulence 3:635–646

  42. Jacobsen ID, Brunke S, Seider K, Schwarzmuller T, Firon A et al (2010) Candida glabrata persistence in mice does not depend on host immunosuppression and is unaffected by fungal amino acid auxotrophy. Infect Immun 78:1066–1077

    Article  PubMed  CAS  Google Scholar 

  43. Cheng SC, Joosten LA, Kullberg BJ, Netea MG (2012) Interplay between Candida albicans and the mammalian innate host defense. Infect Immun 80:1304–1313

    Article  PubMed  CAS  Google Scholar 

  44. Qian Q, Jutila MA, Van Rooijen N, Cutler JE (1994) Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. J Immunol 152:5000–5008

    PubMed  CAS  Google Scholar 

  45. Klis FM, de Groot P, Hellingwerf K (2001) Molecular organization of the cell wall of Candida albicans. Med Mycol 39(Suppl 1):1–8

    PubMed  CAS  Google Scholar 

  46. Netea MG, Brown GD, Kullberg BJ, Gow NA (2008) An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol 6:67–78

    Article  PubMed  CAS  Google Scholar 

  47. Sato K, Yang XL, Yudate T, Chung JS, Wu J et al (2006) Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. J Biol Chem 281:38854–38866

    Article  PubMed  CAS  Google Scholar 

  48. Jouault T, El Abed-El BehiM, Martinez-Esparza M, Breuilh L, Trinel PA et al (2006) Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling. J Immunol 177:4679–4687

    PubMed  CAS  Google Scholar 

  49. Netea MG, Gow NA, Munro CA, Bates S, Collins C et al (2006) Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J Clin Invest 116:1642–1650

    Article  PubMed  CAS  Google Scholar 

  50. Jouault T, Ibata-Ombetta S, Takeuchi O, Trinel PA, Sacchetti P et al (2003) Candida albicans phospholipomannan is sensed through toll-like receptors. J Infect Dis 188:165–172

    Article  PubMed  CAS  Google Scholar 

  51. Lewis LE, Bain JM, Lowes C, Gillespie C, Rudkin FM et al (2012) Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants. PLoS Pathog 8:e1002578

    Article  PubMed  CAS  Google Scholar 

  52. Sheth CC, Hall R, Lewis L, Brown AJ, Odds FC et al (2011) Glycosylation status of the C. albicans cell wall affects the efficiency of neutrophil phagocytosis and killing but not cytokine signaling. Med Mycol 49:513–524

    PubMed  CAS  Google Scholar 

  53. McKenzie CG, Koser U, Lewis LE, Bain JM, Mora-Montes HM et al (2010) Contribution of Candida albicans cell wall components to recognition by and escape from murine macrophages. Infect Immun 78:1650–1658

    Article  PubMed  CAS  Google Scholar 

  54. Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L et al (2002) The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol 169:3876–3882

    PubMed  CAS  Google Scholar 

  55. Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL et al (2002) Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med 196:407–412

    Article  PubMed  CAS  Google Scholar 

  56. Esteban A, Popp MW, Vyas VK, Strijbis K, Ploegh HL et al (2011) Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages. Proc Natl Acad Sci USA 108:14270–14275

    Article  PubMed  CAS  Google Scholar 

  57. Bugarcic A, Hitchens K, Beckhouse AG, Wells CA, Ashman RB et al (2008) Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans. Glycobiology 18:679–685

    Article  PubMed  CAS  Google Scholar 

  58. Kasperkovitz PV, Khan NS, Tam JM, Mansour MK, Davids PJ et al (2011) Toll-like receptor 9 modulates macrophage antifungal effector function during innate recognition of Candida albicans and Saccharomyces cerevisiae. Infect Immun 79:4858–4867

    Article  PubMed  CAS  Google Scholar 

  59. Biondo C, Malara A, Costa A, Signorino G, Cardile F et al (2012) Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis. Eur J Immunol 42:2632–2643

    Article  PubMed  CAS  Google Scholar 

  60. Herre J, Marshall AS, Caron E, Edwards AD, Williams DL et al (2004) Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood 104:4038–4045

    Article  PubMed  CAS  Google Scholar 

  61. Heinsbroek SE, Taylor PR, Martinez FO, Martinez-Pomares L, Brown GD et al (2008) Stage-specific sampling by pattern recognition receptors during Candida albicans phagocytosis. PLoS Pathog 4:e1000218

    Article  PubMed  CAS  Google Scholar 

  62. Romani L, Montagnoli C, Bozza S, Perruccio K, Spreca A et al (2004) The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicans. Int Immunol 16:149–161

    Article  PubMed  CAS  Google Scholar 

  63. Cambi A, Gijzen K, de Vries JM, Torensma R, Joosten B et al (2003) The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells. Eur J Immunol 33:532–538

    Article  PubMed  CAS  Google Scholar 

  64. Brouwer N, Dolman KM, van Houdt M, Sta M, Roos D et al (2008) Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. J Immunol 180:4124–4132

    PubMed  CAS  Google Scholar 

  65. Li D, Dong B, Tong Z, Wang Q, Liu W et al (2012) MBL-mediated opsonophagocytosis of Candida albicans by human neutrophils Is coupled with intracellular dectin-1-triggered ros production. PLoS ONE 7:e50589

    Article  PubMed  CAS  Google Scholar 

  66. Rubin-Bejerano I, Abeijon C, Magnelli P, Grisafi P, Fink GR (2007) Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component. Cell Host Microbe 2:55–67

    Article  PubMed  CAS  Google Scholar 

  67. Soloviev DA, Fonzi WA, Sentandreu R, Pluskota E, Forsyth CB et al (2007) Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2. J Immunol 178:2038–2046

    PubMed  CAS  Google Scholar 

  68. Soloviev DA, Jawhara S, Fonzi WA (2011) Regulation of innate immune response to Candida albicans infections by alphaMbeta2-Pra1p interaction. Infect Immun 79:1546–1558

    Article  PubMed  CAS  Google Scholar 

  69. Jawhara S, Pluskota E, Verbovetskiy D, Skomorovska-Prokvolit O, Plow EF et al (2012) Integrin alpha(X)beta(2) is a leukocyte receptor for Candida albicans and is essential for protection against fungal infections. J Immunol 189:2468–2477

    Article  PubMed  CAS  Google Scholar 

  70. Kuhn DM, Vyas VK (2012) The Candida glabrata adhesin Epa1p causes adhesion, phagocytosis, and cytokine secretion by innate immune cells. FEMS Yeast Res 12:398–414

    Article  PubMed  CAS  Google Scholar 

  71. Swanson JA (2008) Shaping cups into phagosomes and macropinosomes. Nat Rev Mol Cell Biol 9:639–649

    Article  PubMed  CAS  Google Scholar 

  72. Vieira OV, Botelho RJ, Grinstein S (2002) Phagosome maturation: aging gracefully. Biochem J 366:689–704

    PubMed  CAS  Google Scholar 

  73. Newman SL, Bhugra B, Holly A, Morris RE (2005) Enhanced killing of Candida albicans by human macrophages adherent to type 1 collagen matrices via induction of phagolysosomal fusion. Infect Immun 73:770–777

    Article  PubMed  CAS  Google Scholar 

  74. Lee WL, Harrison RE, Grinstein S (2003) Phagocytosis by neutrophils. Microbes Infect 5:1299–1306

    Article  PubMed  CAS  Google Scholar 

  75. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489

    Article  PubMed  CAS  Google Scholar 

  76. Segal BH, Grimm MJ, Khan AN, Han W, Blackwell TS (2012) Regulation of innate immunity by NADPH oxidase. Free Radic Biol Med 53:72–80

    Article  PubMed  CAS  Google Scholar 

  77. Fang FC (2004) Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol 2:820–832

    Article  PubMed  CAS  Google Scholar 

  78. Klebanoff SJ (2005) Myeloperoxidase: friend and foe. J Leukoc Biol 77:598–625

    Article  PubMed  CAS  Google Scholar 

  79. Winterbourn CC, Hampton MB, Livesey JH, Kettle AJ (2006) Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome: implications for microbial killing. J Biol Chem 281:39860–39869

    Article  PubMed  CAS  Google Scholar 

  80. Donini M, Zenaro E, Tamassia N, Dusi S (2007) NADPH oxidase of human dendritic cells: role in Candida albicans killing and regulation by interferons, dectin-1 and CD206. Eur J Immunol 37:1194–1203

    Article  PubMed  CAS  Google Scholar 

  81. Aratani Y, Koyama H, Nyui S, Suzuki K, Kura F et al (1999) Severe impairment in early host defense against Candida albicans in mice deficient in myeloperoxidase. Infect Immun 67:1828–1836

    PubMed  CAS  Google Scholar 

  82. Sasada M, Johnston RB Jr (1980) Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. J Exp Med 152:85–98

    Article  PubMed  CAS  Google Scholar 

  83. Hibbs JB Jr (2002) Infection and nitric oxide. J Infect Dis 185(Suppl 1):S9–S17

    Article  PubMed  CAS  Google Scholar 

  84. Vázquez-Torres A, Jones-Carson J, Balish E (1996) Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing macrophages. Infect Immun 64:3127–3133

    PubMed  Google Scholar 

  85. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y et al (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535

    Article  PubMed  CAS  Google Scholar 

  86. Urban CF, Reichard U, Brinkmann V, Zychlinsky A (2006) Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol 8:668–676

    Article  PubMed  CAS  Google Scholar 

  87. Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C et al (2009) Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog 5:e1000639

    Article  PubMed  CAS  Google Scholar 

  88. Rubin-Bejerano I, Fraser I, Grisafi P, Fink GR (2003) Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans. Proc Natl Acad Sci USA 100:11007–11012

    Article  PubMed  CAS  Google Scholar 

  89. Fradin C, Kretschmar M, Nichterlein T, Gaillardin C, d’Enfert C et al (2003) Stage-specific gene expression of Candida albicans in human blood. Mol Microbiol 47:1523–1543

    Article  PubMed  CAS  Google Scholar 

  90. Fernández-Arenas E, Cabezón V, Bermejo C, Arroyo J, Nombela C et al (2007) Integrated proteomics and genomics strategies bring new insight into Candida albicans response upon macrophage interaction. Mol Cell Proteomics 6:460–478

    PubMed  Google Scholar 

  91. Kaur R, Ma B, Cormack BP (2007) A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata. Proc Natl Acad Sci USA 104:7628–7633

    Article  PubMed  CAS  Google Scholar 

  92. Rai MN, Balusu S, Gorityala N, Dandu L, Kaur R (2012) Functional genomic analysis of Candida glabrata-macrophage interaction: role of chromatin remodeling in virulence. PLoS Pathog 8:e1002863

    Article  PubMed  CAS  Google Scholar 

  93. Seider K, Brunke S, Schild L, Jablonowski N, Wilson D et al (2011) The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation. J Immunol 187:3072–3086

    Article  PubMed  CAS  Google Scholar 

  94. Gantner BN, Simmons RM, Underhill DM (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24:1277–1286

    Article  PubMed  CAS  Google Scholar 

  95. Wozniok I, Hornbach A, Schmitt C, Frosch M, Einsele H et al (2008) Induction of ERK-kinase signalling triggers morphotype-specific killing of Candida albicans filaments by human neutrophils. Cell Microbiol 10:807–820

    Article  PubMed  CAS  Google Scholar 

  96. Vylkova S, Carman AJ, Danhof HA, Collette JR, Zhou H et al (2011) The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH. MBio 2:e00055–e00011

    Google Scholar 

  97. Lorenz MC, Bender JA, Fink GR (2004) Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3:1076–1087

    Article  PubMed  CAS  Google Scholar 

  98. Moran GP, MacCallum DM, Spiering MJ, Coleman DC, Sullivan DJ (2007) Differential regulation of the transcriptional repressor NRG1 accounts for altered host-cell interactions in Candida albicans and Candida dubliniensis. Mol Microbiol 66:915–929

    Article  PubMed  CAS  Google Scholar 

  99. Calcagno AM, Bignell E, Warn P, Jones MD, Denning DW et al (2003) Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation. Mol Microbiol 50:1309–1318

    Article  PubMed  CAS  Google Scholar 

  100. Otto V, Howard DH (1976) Further studies on the intracellular behavior of Torulopsis glabrata. Infect Immun 14:433–438

    PubMed  CAS  Google Scholar 

  101. Barelle CJ, Priest CL, MacCallum DM, Gow NA, Odds FC et al (2006) Niche-specific regulation of central metabolic pathways in a fungal pathogen. Cell Microbiol 8:961–971

    Article  PubMed  CAS  Google Scholar 

  102. Miramón P, Dunker C, Windecker H, Bohovych IM, Brown AJ et al (2012) Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress. PLoS ONE 7:e52850

    Article  PubMed  CAS  Google Scholar 

  103. Nguyen LN, Trofa D, Nosanchuk JD (2009) Fatty acid synthase impacts the pathobiology of Candida parapsilosis in vitro and during mammalian infection. PLoS ONE 4:e8421

    Article  PubMed  CAS  Google Scholar 

  104. Gacser A, Trofa D, Schafer W, Nosanchuk JD (2007) Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence. J Clin Invest 117:3049–3058

    Article  PubMed  CAS  Google Scholar 

  105. Nagy I, Filkor K, Nemeth T, Hamari Z, Vagvolgyi C et al (2011) In vitro interactions of Candida parapsilosis wild type and lipase deficient mutants with human monocyte derived dendritic cells. BMC Microbiol 11:122

    Article  PubMed  CAS  Google Scholar 

  106. Ghosh S, Navarathna DH, Roberts DD, Cooper JT, Atkin AL et al (2009) Arginine-induced germ tube formation in Candida albicans is essential for escape from murine macrophage line RAW 264.7. Infect Immun 77:1596–1605

    Article  PubMed  CAS  Google Scholar 

  107. Jiménez-López C, Collette JR, Brothers KM, Shepardson KM, Cramer RA et al (2012) Candida albicans induces arginine biosynthetic genes in response to host-derived reactive oxygen species. Eukaryot Cell 12(1):91–100

    Google Scholar 

  108. Biswas K, Morschhauser J (2005) The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. Mol Microbiol 56:649–669

    Article  PubMed  CAS  Google Scholar 

  109. Palmer GE, Kelly MN, Sturtevant JE (2007) Autophagy in the pathogen Candida albicans. Microbiology 153:51–58

    Article  PubMed  CAS  Google Scholar 

  110. Roetzer A, Gratz N, Kovarik P, Schuller C (2010) Autophagy supports Candida glabrata survival during phagocytosis. Cell Microbiol 12:199–216

    Article  PubMed  CAS  Google Scholar 

  111. Nevitt T, Thiele DJ (2011) Host iron withholding demands siderophore utilization for Candida glabrata to survive macrophage killing. PLoS Pathog 7:e1001322

    Article  PubMed  CAS  Google Scholar 

  112. Smith DA, Nicholls S, Morgan BA, Brown AJ, Quinn J (2004) A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans. Mol Biol Cell 15:4179–4190

    Article  PubMed  CAS  Google Scholar 

  113. Smith DA, Morgan BA, Quinn J (2010) Stress signalling to fungal stress-activated protein kinase pathways. FEMS Microbiol Lett 306:1–8

    Article  PubMed  CAS  Google Scholar 

  114. Wang Y, Cao YY, Jia XM, Cao YB, Gao PH et al (2006) Cap1p is involved in multiple pathways of oxidative stress response in Candida albicans. Free Radic Biol Med 40:1201–1209

    Article  PubMed  CAS  Google Scholar 

  115. Znaidi S, Barker KS, Weber S, Alarco AM, Liu TT et al (2009) Identification of the Candida albicans Cap1p regulon. Eukaryot Cell 8:806–820

    Article  PubMed  CAS  Google Scholar 

  116. Arana DM, Alonso-Monge R, Du C, Calderone R, Pla J (2007) Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans. Cell Microbiol 9:1647–1659

    Article  PubMed  CAS  Google Scholar 

  117. Cuéllar-Cruz M, Briones-Martin-del-Campo M, Canas-Villamar I, Montalvo-Arredondo J, Riego-Ruiz L et al (2008) High resistance to oxidative stress in the fungal pathogen Candida glabrata is mediated by a single catalase, Cta1p, and is controlled by the transcription factors Yap1p, Skn7p, Msn2p, and Msn4p. Eukaryot Cell 7:814–825

    Article  PubMed  CAS  Google Scholar 

  118. Kaloriti D, Tillmann A, Cook E, Jacobsen M, You T et al (2012) Combinatorial stresses kill pathogenic Candida species. Med Mycol 50(7):699–709

    Google Scholar 

  119. Roetzer A, Gregori C, Jennings AM, Quintin J, Ferrandon D et al (2008) Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors. Mol Microbiol 69:603–620

    Article  PubMed  CAS  Google Scholar 

  120. Hwang CS, Rhie GE, Oh JH, Huh WK, Yim HS et al (2002) Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence. Microbiology 148:3705–3713

    PubMed  CAS  Google Scholar 

  121. Chaves GM, Bates S, MacCallum DM, Odds FC (2007) Candida albicans GRX2, encoding a putative glutaredoxin, is required for virulence in a murine model. Genet Mol Res 6:1051–1063

    PubMed  CAS  Google Scholar 

  122. Fitzpatrick DA, Logue ME, Stajich JE, Butler G (2006) A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis. BMC Evol Biol 6:99

    Article  PubMed  CAS  Google Scholar 

  123. Martchenko M, Alarco AM, Harcus D, Whiteway M (2004) Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene. Mol Biol Cell 15:456–467

    Article  PubMed  CAS  Google Scholar 

  124. Heilmann CJ, Sorgo AG, Siliakus AR, Dekker HL, Brul S et al (2011) Hyphal induction in the human fungal pathogen Candida albicans reveals a characteristic wall protein profile. Microbiology 157:2297–2307

    Article  PubMed  CAS  Google Scholar 

  125. Frohner IE, Bourgeois C, Yatsyk K, Majer O, Kuchler K (2008) C. albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol Microbiol 71:240–252

    Article  PubMed  CAS  Google Scholar 

  126. Nakagawa Y, Kanbe T, Mizuguchi I (2003) Disruption of the human pathogenic yeast Candida albicans catalase gene decreases survival in mouse-model infection and elevates susceptibility to higher temperature and to detergents. Microbiol Immunol 47:395–403

    PubMed  CAS  Google Scholar 

  127. Enjalbert B, MacCallum DM, Odds FC, Brown AJ (2007) Niche-specific activation of the oxidative stress response by the pathogenic fungus Candida albicans. Infect Immun 75:2143–2151

    Article  PubMed  CAS  Google Scholar 

  128. Wysong DR, Christin L, Sugar AM, Robbins PW, Diamond RD (1998) Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect Immun 66:1953–1961

    PubMed  CAS  Google Scholar 

  129. Avery AM, Avery SV (2001) Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases. J Biol Chem 276:33730–33735

    Article  PubMed  CAS  Google Scholar 

  130. Avery AM, Willetts SA, Avery SV (2004) Genetic dissection of the phospholipid hydroperoxidase activity of yeast gpx3 reveals its functional importance. J Biol Chem 279:46652–46658

    Article  PubMed  CAS  Google Scholar 

  131. Yadav AK, Desai PR, Rai MN, Kaur R, Ganesan K et al (2011) Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: essential in C. glabrata, and essential for virulence in C. albicans. Microbiology 157:484–495

    Article  PubMed  CAS  Google Scholar 

  132. da Silva DantasA, Patterson MJ, Smith DA, Maccallum DM, Erwig LP et al (2010) Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans. Mol Cell Biol 30:4550–4563

    Article  CAS  Google Scholar 

  133. Martínez-Esparza M, Aguinaga A, González-Párraga P, García-Peñarrubia P, Jouault T et al (2007) Role of trehalose in resistance to macrophage killing: study with a tps1/tps1 trehalose-deficient mutant of Candida albicans. Clin Microbiol Infect 13:384–394

    Article  PubMed  Google Scholar 

  134. Mayer FL, Wilson D, Jacobsen ID, Miramón P, Slesiona S et al (2012) Small but crucial: the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans. PLoS ONE 7:e38584

    Article  PubMed  CAS  Google Scholar 

  135. Roetzer A, Klopf E, Gratz N, Marcet-Houben M, Hiller E et al (2011) Regulation of Candida glabrata oxidative stress resistance is adapted to host environment. FEBS Lett 585:319–327

    Article  PubMed  CAS  Google Scholar 

  136. Hromatka BS, Noble SM, Johnson AD (2005) Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence. Mol Biol Cell 16:4814–4826

    Article  PubMed  CAS  Google Scholar 

  137. Ullmann BD, Myers H, Chiranand W, Lazzell AL, Zhao Q et al (2004) Inducible defense mechanism against nitric oxide in Candida albicans. Eukaryot Cell 3:715–723

    Article  PubMed  CAS  Google Scholar 

  138. Chiranand W, McLeod I, Zhou H, Lynn JJ, Vega LA et al (2008) CTA4 transcription factor mediates induction of nitrosative stress response in Candida albicans. Eukaryot Cell 7:268–278

    Article  PubMed  CAS  Google Scholar 

  139. Sellam A, Tebbji F, Whiteway M, Nantel A (2012) A novel role for the transcription factor Cwt1p as a negative regulator of nitrosative stress in Candida albicans. PLoS ONE 7:e43956

    Article  PubMed  CAS  Google Scholar 

  140. Pereira HA, Tsyshevskaya-Hoover I, Hinsley H, Logan S, Nguyen M et al (2010) Candidacidal activity of synthetic peptides based on the antimicrobial domain of the neutrophil-derived protein, CAP37. Med Mycol 48:263–272

    Article  PubMed  CAS  Google Scholar 

  141. den Hertog AL, van Marle J, van Veen HA, Van’t Hof W, Bolscher JG et al (2005) Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. Biochem J 388:689–695

    Article  CAS  Google Scholar 

  142. Andrés MT, Viejo-Díaz M, Fierro JF (2008) Human lactoferrin induces apoptosis-like cell death in Candida albicans: critical role of K+ -channel-mediated K+ efflux. Antimicrob Agents Chemother 52:4081–4088

    Article  PubMed  CAS  Google Scholar 

  143. Wheeler RT, Kombe D, Agarwala SD, Fink GR (2008) Dynamic, morphotype-specific Candida albicans beta-glucan exposure during infection and drug treatment. PLoS Pathog 4:e1000227

    Article  PubMed  CAS  Google Scholar 

  144. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM (2003) Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med 197:1107–1117

    Article  PubMed  CAS  Google Scholar 

  145. Dennehy KM, Willment JA, Williams DL, Brown GD (2009) Reciprocal regulation of IL-23 and IL-12 following co-activation of Dectin-1 and TLR signaling pathways. Eur J Immunol 39:1379–1386

    Article  PubMed  CAS  Google Scholar 

  146. Crowe JD, Sievwright IK, Auld GC, Moore NR, Gow NA et al (2003) Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. Mol Microbiol 47:1637–1651

    Article  PubMed  CAS  Google Scholar 

  147. Poltermann S, Kunert A, von der Heide M, Eck R, Hartmann A et al (2007) Gpm1p is a factor H-, FHL-1-, and plasminogen-binding surface protein of Candida albicans. J Biol Chem 282:37537–37544

    Article  PubMed  CAS  Google Scholar 

  148. Luo S, Poltermann S, Kunert A, Rupp S, Zipfel PF (2009) Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor H, FHL-1 and plasminogen binding surface protein. Mol Immunol 47:541–550

    Article  PubMed  CAS  Google Scholar 

  149. Luo S, Hoffmann R, Skerka C, Zipfel PF (2012) Glycerol-3-phosphate dehydrogenase 2 is a novel factor h, fhl-1 and plasminogen binding surface protein of Candida albicans. J Infect Dis

  150. Luo S, Hartmann A, Dahse HM, Skerka C, Zipfel PF (2010) Secreted pH-regulated antigen 1 of Candida albicans blocks activation and conversion of complement C3. J Immunol 185:2164–2173

    Article  PubMed  CAS  Google Scholar 

  151. Albrecht A, Felk A, Pichova I, Naglik JR, Schaller M et al (2006) Glycosylphosphatidylinositol-anchored proteases of Candida albicans target proteins necessary for both cellular processes and host-pathogen interactions. J Biol Chem 281:688–694

    Article  PubMed  CAS  Google Scholar 

  152. Schild L, Heyken A, de Groot PW, Hiller E, Mock M et al (2011) Proteolytic cleavage of covalently linked cell wall proteins by Candida albicans Sap9 and Sap10. Eukaryot Cell 10:98–109

    Article  PubMed  CAS  Google Scholar 

  153. Borg-von Zepelin M, Beggah S, Boggian K, Sanglard D, Monod M (1998) The expression of the secreted aspartyl proteinases Sap4 to Sap6 from Candida albicans in murine macrophages. Mol Microbiol 28:543–554

    Article  PubMed  CAS  Google Scholar 

  154. Horvath P, Nosanchuk JD, Hamari Z, Vagvolgyi C, Gacser A (2012) The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence. J Infect Dis 205:923–933

    Article  PubMed  CAS  Google Scholar 

  155. Klengel T, Liang WJ, Chaloupka J, Ruoff C, Schroppel K et al (2005) Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr Biol 15:2021–2026

    Article  PubMed  CAS  Google Scholar 

  156. Fernández-Arenas E, Bleck CK, Nombela C, Gil C, Griffiths G et al (2009) Candida albicans actively modulates intracellular membrane trafficking in mouse macrophage phagosomes. Cell Microbiol 11:560–589

    Article  PubMed  CAS  Google Scholar 

  157. Ibata-Ombetta S, Idziorek T, Trinel PA, Poulain D, Jouault T (2003) Candida albicans phospholipomannan promotes survival of phagocytosed yeasts through modulation of bad phosphorylation and macrophage apoptosis. J Biol Chem 278:13086–13093

    Article  PubMed  CAS  Google Scholar 

  158. García-Rodas R, González-Camacho F, Rodríguez-Tudela JL, Cuenca-Estrella M, Zaragoza O (2011) The interaction between Candida krusei and murine macrophages results in multiple outcomes, including intracellular survival and escape from killing. Infect Immun 79:2136–2144

    Article  PubMed  CAS  Google Scholar 

  159. Wellington M, Dolan K, Krysan DJ (2009) Live Candida albicans suppresses production of reactive oxygen species in phagocytes. Infect Immun 77:405–413

    Article  PubMed  CAS  Google Scholar 

  160. Lopes da Rosa J, Boyartchuk VL, Zhu LJ, Kaufman PD (2010) Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis. Proc Natl Acad Sci USA 107:1594–1599

    Article  PubMed  CAS  Google Scholar 

  161. Lu Y, Su C, Wang A, Liu H (2011) Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance. PLoS Biol 9:e1001105

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are indebted to the European Commission for funding the FINSysB Marie Curie Initial Training Network (PITN-GA-2008-214004) and the Deutsche Forschungsgemeinschaft (DFG Hu 528/15-1). We thank Franziska Gerwien for providing microphotographs for Fig. 1 and Duncan Wilson for critical reading of the manuscript. We thank all members of the Department of Microbial Pathogenicity Mechanisms for helpful discussions.

Author information

Authors and Affiliations

  1. Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute, Beutenbergstrasse 11a, 07745, Jena, Germany

    Pedro Miramón, Lydia Kasper & Bernhard Hube

  2. Center for Sepsis Control and Care, Universitätsklinikum Jena, Jena, Germany

    Bernhard Hube

  3. Friedrich Schiller University, Jena, Germany

    Bernhard Hube

Authors
  1. Pedro Miramón
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lydia Kasper
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernhard Hube
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernhard Hube.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miramón, P., Kasper, L. & Hube, B. Thriving within the host: Candida spp. interactions with phagocytic cells. Med Microbiol Immunol 202, 183–195 (2013). https://doi.org/10.1007/s00430-013-0288-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-013-0288-z

Keywords

Search

Navigation