1932

Abstract

Fungi are ubiquitous in our environment, and a healthy immune system is essential to maintain adequate protection from fungal infections. When this protection breaks down, superficial and invasive fungal infections cause diseases that range from irritating to life-threatening. Millions of people worldwide develop invasive infections during their lives, and mortality for these infections often exceeds 50%. Nevertheless, we are normally colonized with many of the same disease-causing fungi (e.g., on the skin or in the gut). Recent research is dramatically expanding our understanding of the mechanisms by which our immune systems interact with these organisms in health and disease. In this review, we discuss what is currently known about where and how the immune system interacts with common fungi.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-052016-100342
2017-01-24
2024-12-02
Loading full text...

Full text loading...

/deliver/fulltext/pathol/12/1/annurev-pathol-052016-100342.html?itemId=/content/journals/10.1146/annurev-pathol-052016-100342&mimeType=html&fmt=ahah

Literature Cited

  1. Drummond RA, Gaffen SL, Hise AG, Brown GD. 1.  2015. Innate defense against fungal pathogens. Cold Spring Harb. Perspect. Med. 5:a019620 [Google Scholar]
  2. Netea MG, Joosten LA, van der Meer JW, Kullberg BJ, van de Veerdonk FL. 2.  2015. Immune defence against Candida fungal infections. Nat. Rev. Immunol. 15:630–42 [Google Scholar]
  3. Rapaka RR, Ricks DM, Alcorn JF, Chen K, Khader SA. 3.  et al. 2010. Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina. J. Exp. Med. 207:2907–19 [Google Scholar]
  4. Seed PC. 4.  2015. The human mycobiome. Cold Spring Harb. Perspect. Med. 5:a019810 [Google Scholar]
  5. Underhill DM, Iliev ID. 5.  2014. The mycobiota: interactions between commensal fungi and the host immune system. Nat. Rev. Immunol. 14:405–16 [Google Scholar]
  6. Ibrahim AS, Kontoyiannis DP. 6.  2013. Update on mucormycosis pathogenesis. Curr. Opin. Infect. Dis. 26:508–15 [Google Scholar]
  7. Johnson L, Gaab EM, Sanchez J, Bui PQ, Nobile CJ. 7.  et al. 2014. Valley fever: danger lurking in a dust cloud. Microbes Infect 16:591–600 [Google Scholar]
  8. Horwath MC, Fecher RA, Deepe GS Jr.. 8.  2015. Histoplasma capsulatum, lung infection and immunity. Future Microbiol 10:967–75 [Google Scholar]
  9. Rohatgi S, Pirofski LA. 9.  2015. Host immunity to Cryptococcus neoformans. Future Microbiol 10:565–81 [Google Scholar]
  10. Tang J, Iliev ID, Brown J, Underhill DM, Funari VA. 10.  2015. Mycobiome: approaches to analysis of intestinal fungi. J. Immunol. Methods 421:112–21 [Google Scholar]
  11. Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M. 11.  et al. 2010. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLOS Pathog 6:e1000713 [Google Scholar]
  12. Dupuy AK, David MS, Li L, Heider TN, Peterson JD. 12.  et al. 2014. Redefining the human oral mycobiome with improved practices in amplicon-based taxonomy: discovery of Malassezia as a prominent commensal. PLOS ONE 9:e90899 [Google Scholar]
  13. Dollive S, Chen YY, Grunberg S, Bittinger K, Hoffmann C. 13.  et al. 2013. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PLOS ONE 8:e71806 [Google Scholar]
  14. Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN. 14.  et al. 2012. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336:1314–17 [Google Scholar]
  15. Sokol H, Leducq V, Aschard H, Pham HP, Jegou S. 15.  et al. 2016. Fungal microbiota dysbiosis in IBD. Gut In press. doi:10.1136/gutjnl-2015-310746. [Google Scholar]
  16. Lewis JD, Chen EZ, Baldassano RN, Otley AR, Griffiths AM. 16.  et al. 2015. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease. Cell Host Microbe 18:489–500 [Google Scholar]
  17. Chehoud C, Albenberg LG, Judge C, Hoffmann C, Grunberg S. 17.  et al. 2015. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm. Bowel Dis. 21:1948–56 [Google Scholar]
  18. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS. 18.  et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65 [Google Scholar]
  19. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T. 19.  et al. 2011. Enterotypes of the human gut microbiome. Nature 473:174–80 [Google Scholar]
  20. Kullberg BJ, Verweij PE, Akova M, Arendrup MC, Bille J. 20.  et al. 2011. European expert opinion on the management of invasive candidiasis in adults. Clin. Microbiol. Infect. 17:Suppl. 51–12 [Google Scholar]
  21. Gabaldon T, Martin T, Marcet-Houben M, Durrens P, Bolotin-Fukuhara M. 21.  et al. 2013. Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genom 14:623 [Google Scholar]
  22. Angoulvant A, Guitard J, Hennequin C. 22.  2016. Old and new pathogenic Nakaseomyces species: epidemiology, biology, identification, pathogenicity and antifungal resistance. FEMS Yeast Res 16:fov114 [Google Scholar]
  23. Latge JP. 23.  1999. Aspergillus fumigatus and aspergillosis. Clin. Microbiol. Rev. 12:310–50 [Google Scholar]
  24. Thomas PA, Kaliamurthy J. 24.  2013. Mycotic keratitis: epidemiology, diagnosis and management. Clin. Microbiol. Infect. 19:210–20 [Google Scholar]
  25. Pitt JI, Samson RA. 25.  2007. Nomenclatural considerations in naming species of Aspergillus and its teleomorphs. Stud. Mycol. 59:67–70 [Google Scholar]
  26. Nucci M, Anaissie E. 26.  2007. Fusarium infections in immunocompromised patients. Clin. Microbiol. Rev. 20:695–704 [Google Scholar]
  27. Bensch K, Braun U, Groenewald JZ, Crous PW. 27.  2012. The genus Cladosporium. Stud. Mycol. 72:1–401 [Google Scholar]
  28. Sandoval-Denis M, Sutton DA, Martin-Vicente A, Cano-Lira JF, Wiederhold N. 28.  et al. 2015. Cladosporium species recovered from clinical samples in the United States. J. Clin. Microbiol. 53:2990–3000 [Google Scholar]
  29. Vacher G, Niculita-Hirzel H, Roger T. 29.  2015. Immune responses to airborne fungi and non-invasive airway diseases. Semin. Immunopathol. 37:83–96 [Google Scholar]
  30. Amend A. 30.  2014. From dandruff to deep-sea vents: Malassezia-like fungi are ecologically hyper-diverse. PLOS Pathog 10:e1004277 [Google Scholar]
  31. Velegraki A, Cafarchia C, Gaitanis G, Iatta R, Boekhout T. 31.  2015. Malassezia infections in humans and animals: pathophysiology, detection, and treatment. PLOS Pathog 11:e1004523 [Google Scholar]
  32. Hooper LV, Littman DR, Macpherson AJ. 32.  2012. Interactions between the microbiota and the immune system. Science 336:1268–73 [Google Scholar]
  33. McFarland LV. 33.  2010. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J. Gastroenterol. 16:2202–22 [Google Scholar]
  34. McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW. 34.  et al. 1994. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 271:1913–18 [Google Scholar]
  35. Batista TM, Marques ET Jr., Franco GR, Douradinha B. 35.  2014. Draft genome sequence of the probiotic yeast Saccharomyces cerevisiae var. boulardii strain ATCC MYA-796. Genome Announc 2:6e01345–14 [Google Scholar]
  36. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. 36.  1999. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect. Immun 67:302–7 [Google Scholar]
  37. Buts JP, Dekeyser N, Stilmant C, Delem E, Smets F, Sokal E. 37.  2006. Saccharomyces boulardii produces in rat small intestine a novel protein phosphatase that inhibits Escherichia coli endotoxin by dephosphorylation. Pediatr. Res 60:24–29 [Google Scholar]
  38. Ducluzeau R, Bensaada M. 38.  1982. Effet compare de l'administration unique ou en continu de Saccharomyces boulardii sur l'etablissement de diverses souches de Candida dans le tractus digestif de souris gnotoxeniques [Comparative effect of a single or continuous administration of Saccharomyces boulardii on the establishment of various strains of Candida in the digestive tract of gnotobiotic mice]. Ann. Microbiol 133:491–501 [Google Scholar]
  39. Zbinden R, Gonczi EE, Altwegg M. 39.  1999. Inhibition of Saccharomyces boulardii (nom. inval.) on cell invasion of Salmonella typhimurium and Yersinia enterocolitica. Microb. Ecol. Health Dis 11:158–62 [Google Scholar]
  40. Qamar A, Aboudola S, Warny M, Michetti P, Pothoulakis C. 40.  et al. 2001. Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice. Infect. Immun 69:2762–65 [Google Scholar]
  41. Thomas S, Metzke D, Schmitz J, Dorffel Y, Baumgart DC. 41.  2011. Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid dendritic cells from patients with Crohn's disease and ulcerative colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 301:G1083–92 [Google Scholar]
  42. Guslandi M, Mezzi G, Sorghi M, Testoni PA. 42.  2000. Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig. Dis. Sci. 45:1462–64 [Google Scholar]
  43. Plein K, Hotz J. 43.  1993. Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to chronic diarrhea—a pilot study. Z. Gastroenterol. 31:129–34 [Google Scholar]
  44. Guslandi M, Giollo P, Testoni PA. 44.  2003. A pilot trial of Saccharomyces boulardii in ulcerative colitis. Eur. J. Gastroenterol. Hepatol. 15:697–98 [Google Scholar]
  45. Dalmasso G, Cottrez F, Imbert V, Lagadec P, Peyron JF. 45.  et al. 2006. Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology 131:1812–25 [Google Scholar]
  46. Jawhara S, Poulain D. 46.  2007. Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis. Med. Mycol 45:691–700 [Google Scholar]
  47. Wu X, Vallance BA, Boyer L, Bergstrom KS, Walker J. 47.  et al. 2008. Saccharomyces boulardii ameliorates Citrobacter rodentium–induced colitis through actions on bacterial virulence factors. Am. J. Physiol. Gastrointest. Liver Physiol 294:G295–306 [Google Scholar]
  48. Takata K, Tomita T, Okuno T, Kinoshita M, Koda T. 48.  et al. 2015. Dietary yeasts reduce inflammation in central nerve system via microflora. Ann. Clin. Transl. Neurol. 2:56–66 [Google Scholar]
  49. Hoffmann C, Dollive S, Grunberg S, Chen J, Li H. 49.  et al. 2013. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLOS ONE 8:e66019 [Google Scholar]
  50. Findley K, Oh J, Yang J, Conlan S, Deming C. 50.  et al. 2013. Topographic diversity of fungal and bacterial communities in human skin. Nature 498:367–70 [Google Scholar]
  51. Rizzetto L, Ifrim DC, Moretti S, Tocci N, Cheng SC. 51.  et al. 2016. Fungal chitin induces trained immunity in human monocytes during cross-talk of the host with Saccharomyces cerevisiae. J. Biol. Chem. 291:7961–72 [Google Scholar]
  52. Quintin J, Saeed S, Martens JH, Giamarellos-Bourboulis EJ, Ifrim DC. 52.  et al. 2012. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12:223–32 [Google Scholar]
  53. Wagener J, Malireddi RK, Lenardon MD, Koberle M, Vautier S. 53.  et al. 2014. Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation. PLOS Pathog 10:e1004050 [Google Scholar]
  54. Zhang Z, Li J, Zheng W, Zhao G, Zhang H. 54.  et al. 2016. Peripheral lymphoid volume expansion and maintenance are controlled by gut microbiota via RALDH+ dendritic cells. Immunity 44:330–42 [Google Scholar]
  55. Bauer H, Horowitz RE, Levenson SM, Popper H. 55.  1963. The response of the lymphatic tissue to the microbial flora. Studies on germfree mice. Am. J. Pathol. 42:471–83 [Google Scholar]
  56. De Jesus M, Rodriguez AE, Yagita H, Ostroff GR, Mantis NJ. 56.  2015. Sampling of Candida albicans and Candida tropicalis by Langerin-positive dendritic cells in mouse Peyer's patches. Immunol. Lett 168:64–72 [Google Scholar]
  57. Wheeler ML, Bar AS, Leal CA, Tang J, Brown J. 57.  et al. 2016. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe 19:6865–73 [Google Scholar]
  58. Bacher P, Kniemeyer O, Schonbrunn A, Sawitzki B, Assenmacher M. 58.  et al. 2014. Antigen-specific expansion of human regulatory T cells as a major tolerance mechanism against mucosal fungi. Mucosal Immunol 7:916–28 [Google Scholar]
  59. Bonifazi P, Zelante T, D'Angelo C, De Luca A, Moretti S. 59.  et al. 2009. Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal Immunol. 2:362–74 [Google Scholar]
  60. Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B. 60.  et al. 2010. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell–like and Foxp3(+) regulatory T cells. Nat. Immunol. 11:846–53 [Google Scholar]
  61. Hauben E, Gregori S, Draghici E, Migliavacca B, Olivieri S. 61.  et al. 2008. Activation of the aryl hydrocarbon receptor promotes allograft-specific tolerance through direct and dendritic cell-mediated effects on regulatory T cells. Blood 112:1214–22 [Google Scholar]
  62. Pierce JV, Kumamoto CA. 62.  2012. Variation in Candida albicans EFG1 expression enables host-dependent changes in colonizing fungal populations. mBio 3:e00117–12 [Google Scholar]
  63. Tyc KM, Herwald SE, Hogan JA, Pierce JV, Klipp E, Kumamoto CA. 63.  2016. The game theory of Candida albicans colonization dynamics reveals host status-responsive gene expression. BMC Syst. Biol. 10:20 [Google Scholar]
  64. Zelante T, Iannitti RG, De Luca A, Arroyo J, Blanco N. 64.  et al. 2012. Sensing of mammalian IL-17A regulates fungal adaptation and virulence. Nat. Commun. 3:683 [Google Scholar]
  65. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. 65.  2012. Hidden killers: human fungal infections. Sci. Transl. Med. 4:165rv13 [Google Scholar]
  66. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. 66.  2004. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39:309–17 [Google Scholar]
  67. Li Z, Jiang C, Dong D, Zhang L, Tian Y. 67.  et al. 2016. The correlation between Candida colonization of distinct body sites and invasive candidiasis in emergency intensive care units: statistical and molecular biological analysis. Mycopathologia 181:7-8475–84 [Google Scholar]
  68. Gouba N, Drancourt M. 68.  2015. Digestive tract mycobiota: a source of infection. Med. Mal. Infect 45:9–16 [Google Scholar]
  69. Miranda LN, van der Heijden IM, Costa SF, Sousa AP, Sienra RA. 69.  et al. 2009. Candida colonisation as a source for candidaemia. J. Hosp. Infect. 72:9–16 [Google Scholar]
  70. Nucci M, Anaissie E. 70.  2001. Revisiting the source of candidemia: skin or gut?. Clin. Infect. Dis. 33:1959–67 [Google Scholar]
  71. Kullberg BJ, Arendrup MC. 71.  2015. Invasive candidiasis. N. Engl. J. Med. 373:1445–56 [Google Scholar]
  72. Sobel JD. 72.  2007. Vulvovaginal candidosis. Lancet 369:1961–71 [Google Scholar]
  73. Tajima M, Sugita T, Nishikawa A, Tsuboi R. 73.  2008. Molecular analysis of Malassezia microflora in seborrheic dermatitis patients: comparison with other diseases and healthy subjects. J. Investig. Dermatol. 128:345–51 [Google Scholar]
  74. Kaneko T, Murotani M, Ohkusu K, Sugita T, Makimura K. 74.  2012. Genetic and biological features of catheter-associated Malassezia furfur from hospitalized adults. Med. Mycol 50:74–80 [Google Scholar]
  75. Curvale-Fauchet N, Botterel F, Legrand P, Guillot J, Bretagne S. 75.  2004. Frequency of intravascular catheter colonization by Malassezia spp. in adult patients. Mycoses 47:491–94 [Google Scholar]
  76. Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP. 76. , Natl. Nosocom. Infections Surveill. System Hospitals. 2002. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin. Infect. Dis 35:627–30 [Google Scholar]
  77. Koh AY, Kohler JR, Coggshall KT, Van Rooijen N, Pier GB. 77.  2008. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLOS Pathog 4:e35 [Google Scholar]
  78. Kozel TR. 78.  1996. Activation of the complement system by pathogenic fungi. Clin. Microbiol. Rev. 9:34–46 [Google Scholar]
  79. Ram S, Lewis LA, Rice PA. 79.  2010. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin. Microbiol. Rev. 23:740–80 [Google Scholar]
  80. van Bruggen R, Drewniak A, Jansen M, van Houdt M, Roos D. 80.  et al. 2009. Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for β-glucan-bearing particles. Mol. Immunol. 47:575–81 [Google Scholar]
  81. Soloviev DA, Fonzi WA, Sentandreu R, Pluskota E, Forsyth CB. 81.  et al. 2007. Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin αMβ2. J. Immunol. 178:2038–46 [Google Scholar]
  82. Uzun O, Ascioglu S, Anaissie EJ, Rex JH. 82.  2001. Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia. Clin. Infect. Dis. 32:1713–17 [Google Scholar]
  83. Lehrer RI, Cline MJ. 83.  1969. Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J. Clin. Investig. 48:1478–88 [Google Scholar]
  84. Winkelstein JA, Marino MC, Johnston RB Jr., Boyle J, Curnutte J. 84.  et al. 2000. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine 79:155–69 [Google Scholar]
  85. Swamydas M, Gao JL, Break TJ, Johnson MD, Jaeger M. 85.  et al. 2016. CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival. Sci. Transl. Med. 8:322ra10 [Google Scholar]
  86. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. 86.  2012. Neutrophil function: from mechanisms to disease. Annu. Rev. Immunol. 30:459–89 [Google Scholar]
  87. Wozniok I, Hornbach A, Schmitt C, Frosch M, Einsele H. 87.  et al. 2008. Induction of ERK-kinase signalling triggers morphotype-specific killing of Candida albicans filaments by human neutrophils. Cell. Microbiol. 10:807–20 [Google Scholar]
  88. Ermert D, Niemiec MJ, Rohm M, Glenthoj A, Borregaard N, Urban CF. 88.  2013. Candida albicans escapes from mouse neutrophils. J. Leukoc. Biol. 94:223–36 [Google Scholar]
  89. Lionakis MS, Lim JK, Lee CC, Murphy PM. 89.  2011. Organ-specific innate immune responses in a mouse model of invasive candidiasis. J. Innate Immun. 3:180–99 [Google Scholar]
  90. Lionakis MS, Fischer BG, Lim JK, Swamydas M, Wan W. 90.  et al. 2012. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis. PLOS Pathog 8:e1002865 [Google Scholar]
  91. Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF. 91.  et al. 2010. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115:1519–29 [Google Scholar]
  92. Hunniger K, Lehnert T, Bieber K, Martin R, Figge MT, Kurzai O. 92.  2014. A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood. PLOS Comput. Biol. 10:e1003479 [Google Scholar]
  93. Qian Q, Jutila MA, Van Rooijen N, Cutler JE. 93.  1994. Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. J. Immunol. 152:5000–8 [Google Scholar]
  94. Ngo LY, Kasahara S, Kumasaka DK, Knoblaugh SE, Jhingran A, Hohl TM. 94.  2014. Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis. J. Infect. Dis. 209:109–19 [Google Scholar]
  95. Lionakis MS, Swamydas M, Fischer BG, Plantinga TS, Johnson MD. 95.  et al. 2013. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. J. Clin. Investig. 123:5035–51 [Google Scholar]
  96. Majer O, Bourgeois C, Zwolanek F, Lassnig C, Kerjaschki D. 96.  et al. 2012. Type I interferons promote fatal immunopathology by regulating inflammatory monocytes and neutrophils during Candida infections. PLOS Pathog 8:e1002811 [Google Scholar]
  97. Bar E, Whitney PG, Moor K, Reis e Sousa C, LeibundGut-Landmann S. 97.  2014. IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells. Immunity 40:117–27 [Google Scholar]
  98. Whitney PG, Bar E, Osorio F, Rogers NC, Schraml BU. 98.  et al. 2014. Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection. PLOS Pathog 10:e1004276 [Google Scholar]
  99. Voigt J, Hunniger K, Bouzani M, Jacobsen ID, Barz D. 99.  et al. 2014. Human natural killer cells acting as phagocytes against Candida albicans and mounting an inflammatory response that modulates neutrophil antifungal activity. J. Infect. Dis. 209:616–26 [Google Scholar]
  100. Lionakis MS. 100.  2012. Genetic susceptibility to fungal infections in humans. Curr. Fungal Infect. Rep. 6:11–22 [Google Scholar]
  101. Lavigne LM, Schopf LR, Chung CL, Maylor R, Sypek JP. 101.  1998. The role of recombinant murine IL-12 and IFN-γ in the pathogenesis of a murine systemic Candida albicans infection. J. Immunol. 160:284–92 [Google Scholar]
  102. Balish E, Wagner RD, Vazquez-Torres A, Pierson C, Warner T. 102.  1998. Candidiasis in interferon-γ knockout (IFN-γ−/−) mice. J. Infect. Dis. 178:478–87 [Google Scholar]
  103. Netea MG, Vonk AG, van den Hoven M, Verschueren I, Joosten LA. 103.  et al. 2003. Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infection. Eur. J. Immunol. 33:3409–17 [Google Scholar]
  104. Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed J. 104.  et al. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42:356–66 [Google Scholar]
  105. Johnson MD, Plantinga TS, van de Vosse E, Velez Edwards DR, Smith PB. 105.  et al. 2012. Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin. Infect. Dis. 54:502–10 [Google Scholar]
  106. Grice EA, Segre JA. 106.  2011. The skin microbiome. Nat. Rev. Microbiol. 9:244–53 [Google Scholar]
  107. Hannigan GD, Meisel JS, Tyldsley AS, Zheng Q, Hodkinson BP. 107.  et al. 2015. The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome. mBio 6:e01578–15 [Google Scholar]
  108. Sanford JA, Gallo RL. 108.  2013. Functions of the skin microbiota in health and disease. Semin. Immunol. 25:370–77 [Google Scholar]
  109. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R. 109.  et al. 2012. Compartmentalized control of skin immunity by resident commensals. Science 337:1115–19 [Google Scholar]
  110. Brasch J, Christophers E. 110.  1993. Azelaic acid has antimycotic properties in vitro. Dermatology 186:55–58 [Google Scholar]
  111. Mayser P. 111.  2015. Medium chain fatty acid ethyl esters—activation of antimicrobial effects by Malassezia enzymes. Mycoses 58:215–19 [Google Scholar]
  112. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G. 112.  et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–50 [Google Scholar]
  113. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J. 113.  et al. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:451–55 [Google Scholar]
  114. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA. 114.  et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–73 [Google Scholar]
  115. Stalhberger T, Simenel C, Clavaud C, Eijsink VG, Jourdain R. 115.  et al. 2014. Chemical organization of the cell wall polysaccharide core of Malassezia restricta. J. Biol. Chem. 289:12647–56 [Google Scholar]
  116. Ishikawa T, Itoh F, Yoshida S, Saijo S, Matsuzawa T. 116.  et al. 2013. Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia. Cell Host Microbe 13:477–88 [Google Scholar]
  117. Selander C, Engblom C, Nilsson G, Scheynius A, Andersson CL. 117.  2009. TLR2/MyD88-dependent and -independent activation of mast cell IgE responses by the skin commensal yeast Malassezia sympodialis. J. Immunol. 182:4208–16 [Google Scholar]
  118. Gaitanis G, Magiatis P, Hantschke M, Bassukas ID, Velegraki A. 118.  2012. The Malassezia genus in skin and systemic diseases. Clin. Microbiol. Rev. 25:106–41 [Google Scholar]
  119. Gaitanis G, Velegraki A, Mayser P, Bassukas ID. 119.  2013. Skin diseases associated with Malassezia yeasts: facts and controversies. Clin. Dermatol. 31:455–63 [Google Scholar]
  120. Mexia N, Gaitanis G, Velegraki A, Soshilov A, Denison MS, Magiatis P. 120.  2015. Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast. Arch. Biochem. Biophys. 571:16–20 [Google Scholar]
  121. Magiatis P, Pappas P, Gaitanis G, Mexia N, Melliou E. 121.  et al. 2013. Malassezia yeasts produce a collection of exceptionally potent activators of the Ah (dioxin) receptor detected in diseased human skin. J. Investig. Dermatol. 133:2023–30 [Google Scholar]
  122. Barouti N, Mainetti C, Fontao L, Sorg O. 122.  2015. L-Tryptophan as a novel potential pharmacological treatment for wound healing via aryl hydrocarbon receptor activation. Dermatology 230:332–39 [Google Scholar]
  123. Bock KW, Kohle C. 123.  2009. The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver. Biol. Chem. 390:1225–35 [Google Scholar]
  124. Di Meglio P, Duarte JH, Ahlfors H, Owens ND, Li Y. 124.  et al. 2014. Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity 40:989–1001 [Google Scholar]
  125. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L. 125.  et al. 2008. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453:106–9 [Google Scholar]
  126. Vlachos C, Schulte BM, Magiatis P, Adema GJ, Gaitanis G. 126.  2012. Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit Toll-like receptor–induced maturation in monocyte-derived dendritic cells. Br. J. Dermatol. 167:496–505 [Google Scholar]
  127. Kadow S, Jux B, Zahner SP, Wingerath B, Chmill S. 127.  et al. 2011. Aryl hydrocarbon receptor is critical for homeostasis of invariant γδ T cells in the murine epidermis. J. Immunol. 187:3104–10 [Google Scholar]
  128. Zhang E, Tanaka T, Tajima M, Tsuboi R, Nishikawa A, Sugita T. 128.  2011. Characterization of the skin fungal microbiota in patients with atopic dermatitis and in healthy subjects. Microbiol. Immunol. 55:625–32 [Google Scholar]
  129. Marcinkiewicz M, Majewski S. 129.  2016. The role of antimicrobial peptides in chronic inflammatory skin diseases. Postęp. Dermatol. Alergol. 33:6–12 [Google Scholar]
  130. Rapala-Kozik M, Bochenska O, Zawrotniak M, Wolak N, Trebacz G. 130.  et al. 2015. Inactivation of the antifungal and immunomodulatory properties of human cathelicidin LL-37 by aspartic proteases produced by the pathogenic yeast Candida albicans. Infect. Immun. 83:2518–30 [Google Scholar]
  131. Lopez CM, Wallich R, Riesbeck K, Skerka C, Zipfel PF. 131.  2014. Candida albicans uses the surface protein Gpm1 to attach to human endothelial cells and to keratinocytes via the adhesive protein vitronectin. PLOS ONE 9:e90796 [Google Scholar]
  132. Ran Y, Yamazaki M, Tsuboi R, Ogawa H. 132.  2014. Adherence and proliferation of keratinocytes cultured with Candida albicans. J. Dermatol. 41:554–56 [Google Scholar]
  133. Mohammed J, Beura LK, Bobr A, Astry B, Chicoine B. 133.  et al. 2016. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.. Nat. Immunol. 17:414–21 [Google Scholar]
  134. Kaplan DH. 134.  2010. In vivo function of Langerhans cells and dermal dendritic cells. Trends Immunol 31:446–51 [Google Scholar]
  135. Igyarto BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M. 135.  et al. 2011. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity 35:260–72 [Google Scholar]
  136. Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. 136.  2015. Nociceptive sensory fibers drive interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity. Immunity 43:515–26 [Google Scholar]
  137. Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A. 137.  et al. 2014. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature 510:157–61 [Google Scholar]
  138. Cassone A, Cauda R. 138.  2012. Candida and candidiasis in HIV-infected patients: where commensalism, opportunistic behavior and frank pathogenicity lose their borders. AIDS 26:1457–72 [Google Scholar]
  139. Mukherjee PK, Chandra J, Retuerto M, Sikaroodi M, Brown RE. 139.  et al. 2014. Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi. PLOS Pathog 10:e1003996 [Google Scholar]
  140. Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX. 140.  et al. 2016. Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532:64–68 [Google Scholar]
  141. Kirkpatrick CH. 141.  2001. Chronic mucocutaneous candidiasis. Pediatr. Infect. Dis. J. 20:197–206 [Google Scholar]
  142. Puel A, Cypowyj S, Marodi L, Abel L, Picard C, Casanova JL. 142.  2012. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr. Opin. Allergy Clin. Immunol. 12:616–22 [Google Scholar]
  143. Gaffen SL, Jain R, Garg AV, Cua DJ. 143.  2014. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat. Rev. Immunol. 14:585–600 [Google Scholar]
  144. Minegishi Y. 144.  2009. Hyper-IgE syndrome. Curr. Opin. Immunol. 21:487–92 [Google Scholar]
  145. Ferwerda B, Ferwerda G, Plantinga TS, Willment JA, van Spriel AB. 145.  et al. 2009. Human dectin-1 deficiency and mucocutaneous fungal infections. N. Engl. J. Med. 361:1760–67 [Google Scholar]
  146. Glocker EO, Hennigs A, Nabavi M, Schaffer AA, Woellner C. 146.  et al. 2009. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361:1727–35 [Google Scholar]
  147. McGovern DP, Kugathasan S, Cho JH. 147.  2015. Genetics of inflammatory bowel diseases. Gastroenterology 149:1163–76 [Google Scholar]
  148. Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D. 148.  et al. 2002. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology 122:1242–47 [Google Scholar]
  149. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP. 149.  et al. 2012. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–24 [Google Scholar]
  150. Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y. 150.  et al. 2011. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat. Genet. 43:1066–73 [Google Scholar]
  151. Ott SJ, Kuhbacher T, Musfeldt M, Rosenstiel P, Hellmig S. 151.  et al. 2008. Fungi and inflammatory bowel diseases: alterations of composition and diversity. Scand. J. Gastroenterol. 43:831–41 [Google Scholar]
  152. Becker KL, Ifrim DC, Quintin J, Netea MG, van de Veerdonk FL. 152.  2015. Antifungal innate immunity: recognition and inflammatory networks. Semin. Immunopathol. 37:107–16 [Google Scholar]
  153. Cunha C, Di Ianni M, Bozza S, Giovannini G, Zagarella S. 153.  et al. 2010. Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient- and donor-dependent mechanisms of antifungal immunity. Blood 116:5394–402 [Google Scholar]
  154. Saijo S, Fujikado N, Furuta T, Chung SH, Kotaki H. 154.  et al. 2007. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat. Immunol. 8:39–46 [Google Scholar]
  155. Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M. 155.  et al. 2007. Dectin-1 is required for β-glucan recognition and control of fungal infection. Nat. Immunol. 8:31–38 [Google Scholar]
  156. Kerscher B, Willment JA, Brown GD. 156.  2013. The Dectin-2 family of C-type lectin-like receptors: an update. Int. Immunol. 25:271–77 [Google Scholar]
  157. Ifrim DC, Bain JM, Reid DM, Oosting M, Verschueren I. 157.  et al. 2014. Role of Dectin-2 for host defense against systemic infection with Candida glabrata. Infect. Immun. 82:1064–73 [Google Scholar]
  158. Zhu LL, Zhao XQ, Jiang C, You Y, Chen XP. 158.  et al. 2013. C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity 39:324–34 [Google Scholar]
  159. Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S. 159.  et al. 2008. The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans. J. Immunol. 180:7404–13 [Google Scholar]
  160. Yamasaki S, Matsumoto M, Takeuchi O, Matsuzawa T, Ishikawa E. 160.  et al. 2009. C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. PNAS 106:1897–902 [Google Scholar]
  161. Sainz J, Lupianez CB, Segura-Catena J, Vazquez L, Rios R. 161.  et al. 2012. Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection. PLOS ONE 7:e32273 [Google Scholar]
  162. de Jong MA, Geijtenbeek TB. 162.  2010. Langerhans cells in innate defense against pathogens. Trends Immunol 31:452–59 [Google Scholar]
  163. Dan JM, Kelly RM, Lee CK, Levitz SM. 163.  2008. Role of the mannose receptor in a murine model of Cryptococcus neoformans infection. Infect. Immun. 76:2362–67 [Google Scholar]
  164. Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Meer JW, Kullberg BJ. 164.  2002. The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J. Infect. Dis. 185:1483–89 [Google Scholar]
  165. Plantinga TS, Johnson MD, Scott WK, van de Vosse E, Velez Edwards DR. 165.  et al. 2012. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J. Infect. Dis. 205:934–43 [Google Scholar]
  166. Kesh S, Mensah NY, Peterlongo P, Jaffe D, Hsu K. 166.  et al. 2005. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann. N. Y. Acad. Sci. 1062:95–103 [Google Scholar]
  167. Zarember KA, Godowski PJ. 167.  2002. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J. Immunol. 168:554–61 [Google Scholar]
  168. Bochud PY, Chien JW, Marr KA, Leisenring WM, Upton A. 168.  et al. 2008. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 359:1766–77 [Google Scholar]
  169. Linden JR, De Paepe ME, Laforce-Nesbitt SS, Bliss JM. 169.  2013. Galectin-3 plays an important role in protection against disseminated candidiasis. Med. Mycol 51:641–51 [Google Scholar]
  170. Chen HY, Liu FT, Yang RY. 170.  2005. Roles of galectin-3 in immune responses. Arch. Immunol. Ther. Exp. 53:497–504 [Google Scholar]
  171. Means TK, Mylonakis E, Tampakakis E, Colvin RA, Seung E. 171.  et al. 2009. Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J. Exp. Med. 206:637–53 [Google Scholar]
  172. Soloviev DA, Jawhara S, Fonzi WA. 172.  2011. Regulation of innate immune response to Candida albicans infections by αMβ2-Pra1p interaction. Infect. Immun. 79:1546–58 [Google Scholar]
  173. Donders GG, Babula O, Bellen G, Linhares IM, Witkin SS. 173.  2008. Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis. BJOG 115:1225–31 [Google Scholar]
  174. Granell M, Urbano-Ispizua A, Suarez B, Rovira M, Fernandez-Aviles F. 174.  et al. 2006. Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation. Exp. Hematol. 34:1435–41 [Google Scholar]
  175. Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O. 175.  et al. 2014. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 370:421–32 [Google Scholar]
  176. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M. 176.  et al. 2002. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:182–86 [Google Scholar]
  177. Garlanda C, Bottazzi B, Bastone A, Mantovani A. 177.  2005. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu. Rev. Immunol. 23:337–66 [Google Scholar]
/content/journals/10.1146/annurev-pathol-052016-100342
Loading
/content/journals/10.1146/annurev-pathol-052016-100342
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error