Skip to main content

Advertisement

SpringerLink
Log in

Host genetics of invasive Aspergillus and Candida infections

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Invasive candidiasis and aspergillosis are major complications in surgical and onco-hematological patients, and still associated with an important morbidity and mortality. A large number of studies highlighted the potential role of host genetic polymorphisms that may influence susceptibility to fungal pathogens, but many were limited by insufficient statistical power, problematic design, and/or lack of replication. However, some relevant polymorphisms are now emerging from well-conducted studies whose associations have been replicated and/or are supported by strong biological evidence. Such polymorphisms together with other biomarkers may play a role in the prediction, diagnosis, and management of severe fungal infections in high-risk patients in the coming years.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Beck-Sague C, Jarvis WR (1993) Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. National Nosocomial Infections Surveillance System. J Infect Dis 167(5):1247–1251

    CAS  PubMed  Google Scholar 

  2. Pagano L, Caira M, Nosari A, Van Lint MT, Candoni A, Offidani M et al (2007) Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study—Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis 45(9):1161–1170. doi:10.1086/522189

    CAS  PubMed  Google Scholar 

  3. Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J et al (2004) Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis Off Publ Infect Dis Soc Am 38(3):311–320

    Google Scholar 

  4. Leroy O, Gangneux JP, Montravers P, Mira JP, Gouin F, Sollet JP et al (2009) Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med 37(5):1612–1618. doi:10.1097/CCM.0b013e31819efac0

    PubMed  Google Scholar 

  5. Calandra TBJ, Schneider R, Mosimann F, Francioli P (1989) Clinical significance of Candida isolated from peritoneum in surgical patients. Lancet 2(8677):1437–1440

    CAS  PubMed  Google Scholar 

  6. Eggimann P, Francioli P, Bille J, Schneider R, Wu MM, Chapuis G et al (1999) Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med 27(6):1066–1072

    CAS  PubMed  Google Scholar 

  7. Prella M, Bille J, Pugnale M, Duvoisin B, Cavassini M, Calandra T et al (2005) Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan antibodies. Diagn Microbiol Infect Dis 51(2):95–101. doi:10.1016/j.diagmicrobio.2004.08.015

    CAS  PubMed  Google Scholar 

  8. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ et al (2010) Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 50(8):1091–1100. doi:10.1086/651263

    PubMed  Google Scholar 

  9. Gavalda J, Len O, San Juan R, Aguado JM, Fortun J, Lumbreras C et al (2005) Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Clin Infect Dis 41(1):52–59. doi:10.1086/430602

    CAS  PubMed  Google Scholar 

  10. Singh N, Husain S, Practice ASTIDCo (2013) Aspergillosis in solid organ transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 13(Suppl 4):228–241. doi:10.1111/ajt.12115

    CAS  Google Scholar 

  11. Eggimann P, Bille J, Marchetti O (2011) Diagnosis of invasive candidiasis in the ICU. Ann Intensive Care 1:37. doi:10.1186/2110-5820-1-37

    PubMed Central  PubMed  Google Scholar 

  12. Maschmeyer G, Haas A, Cornely OA (2007) Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs 67(11):1567–1601

    CAS  PubMed  Google Scholar 

  13. Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J et al (2009) Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis 48(3):265–273. doi:10.1086/595846

    CAS  PubMed  Google Scholar 

  14. Palm NW, Medzhitov R (2009) Pattern recognition receptors and control of adaptive immunity. Immunol Rev 227(1):221–233

    CAS  PubMed  Google Scholar 

  15. Romani L (2011) Immunity to fungal infections. Nat Rev Immunol 11(4):275–288. doi:10.1038/nri2939

    CAS  PubMed  Google Scholar 

  16. Gresnigt MS, Netea MG, van de Veerdonk FL (2012) Pattern recognition receptors and their role in invasive aspergillosis. Ann N Y Acad Sci 1273:60–67. doi:10.1111/j.1749-6632.2012.06759.x

    CAS  PubMed  Google Scholar 

  17. Netea MG, Gow NA, Munro CA, Bates S, Collins C, Ferwerda G et al (2006) Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J Clin Investig 116(6):1642–1650. doi:10.1172/JCI27114

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Jouault T, Ibata-Ombetta S, Takeuchi O, Trinel PA, Sacchetti P, Lefebvre P et al (2003) Candida albicans phospholipomannan is sensed through toll-like receptors. J Infect Dis 188(1):165–172. doi:10.1086/375784

    CAS  PubMed  Google Scholar 

  19. Steele C, Marrero L, Swain S, Harmsen AG, Zheng M, Brown GD et al (2003) Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor. J Exp Med 198(11):1677–1688

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L et al (2002) Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med 196(3):407–412

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H et al (2007) Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol 8(1):31–38

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Said-Sadier N, Padilla E, Langsley G, Ojcius DM (2010) Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS One 5(4):e10008. doi:10.1371/journal.pone.0010008

    PubMed Central  PubMed  Google Scholar 

  23. 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(9):1107–1117

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Dennehy KM, Ferwerda G, Faro-Trindade I, Pyz E, Willment JA, Taylor PR et al (2008) Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur J Immunol 38(2):500–506. doi:10.1002/eji.200737741

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R et al (2002) Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420(6912):182–186. doi:10.1038/nature01195

    CAS  PubMed  Google Scholar 

  26. Lamoth F, Rubino I, Bochud PY (2011) Immunogenetics of invasive aspergillosis. Med Mycol: Off Publ Int Soc Hum Anim Mycol 49(Suppl 1(Suppl 1)):S125–S136. doi:10.3109/13693786.2010.516408

    CAS  Google Scholar 

  27. Gresnigt MS, Becker KL, Smeekens SP, Jacobs CW, Joosten LA, van der Meer JW et al (2013) Aspergillus fumigatus-induced IL-22 is not restricted to a specific Th cell subset and is dependent on complement receptor 3. J Immunol 190(11):5629–5639. doi:10.4049/jimmunol.1202601

    CAS  PubMed  Google Scholar 

  28. Bochud PY, Bochud M, Telenti A, Calandra T (2007) Innate immunogenetics: a tool for exploring new frontiers of host defence. Lancet Infect Dis 7(8):531–542. doi:10.1016/S1473-3099(07)70185-8

    CAS  PubMed  Google Scholar 

  29. Alcais A, Abel L, Casanova JL (2009) Human genetics of infectious diseases: between proof of principle and paradigm. J Clin Investig 119(9):2506–2514. doi:10.1172/JCI38111

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Casanova JL, Abel L (2004) The human model: a genetic dissection of immunity to infection in natural conditions. Nat Rev 4(1):55–66

    CAS  Google Scholar 

  31. Dale DC, Person RE, Bolyard AA, Aprikyan AG, Bos C, Bonilla MA et al (2000) Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 96(7):2317–2322

    CAS  PubMed  Google Scholar 

  32. Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schaffer AA et al (2007) HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet 39(1):86–92. doi:10.1038/ng1940

    CAS  PubMed  Google Scholar 

  33. Fischer A, Lisowska-Grospierre B, Anderson DC, Springer TA (1988) Leukocyte adhesion deficiency: molecular basis and functional consequences. Immunodefic Rev 1(1):39–54

    CAS  PubMed  Google Scholar 

  34. Lionakis MS (2012) Genetic susceptibility to fungal infections in humans. Curr Fung Infect Rep 6(1):11–22. doi:10.1007/s12281-011-0076-4

    Google Scholar 

  35. Lilic D (2012) Unravelling fungal immunity through primary immune deficiencies. Curr Opin Microbiol 15(4):420–426. doi:10.1016/j.mib.2012.06.003

    CAS  PubMed  Google Scholar 

  36. Vinh DC (2011) Insights into human antifungal immunity from primary immunodeficiencies. Lancet Infect Dis 11(10):780–792. doi:10.1016/S1473-3099(11)70217-1

    CAS  PubMed  Google Scholar 

  37. Lanternier F, Cypowyj S, Picard C, Bustamante J, Lortholary O, Casanova JL et al (2013) Primary immunodeficiencies underlying fungal infections. Curr Opin Pediatr 25(6):736–747. doi:10.1097/MOP.0000000000000031

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N et al (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357(16):1608–1619. doi:10.1056/NEJMoa073687

    CAS  PubMed  Google Scholar 

  39. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T et al (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448(7157):1058–1062. doi:10.1038/nature06096

    CAS  PubMed  Google Scholar 

  40. Camargo JF, Lobo SA, Hsu AP, Zerbe CS, Wormser GP, Holland SM (2013) MonoMAC syndrome in a patient with a GATA2 mutation: case report and review of the literature. Clin Infect Dis 57(5):697–699. doi:10.1093/cid/cit368

    PubMed Central  PubMed  Google Scholar 

  41. Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF, Olivier KN et al (2010) Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115(8):1519–1529. doi:10.1182/blood-2009-03-208629

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Levy O, Bourquin JP, McQueen A, Cantor AB, Lachenauer C, Malley R (2002) Fatal disseminated Candida lusitaniae infection in an infant with chronic granulomatous disease. Pediatr Infect Dis J 21(3):262–264

    PubMed  Google Scholar 

  43. Fleischmann J, Church JA, Lehrer RI (1986) Primary Candida meningitis and chronic granulomatous disease. Am J Med Sci 291(5):334–341

    CAS  PubMed  Google Scholar 

  44. Ouederni M, Sanal O, Ikinciogullari A, Tezcan I, Dogu F, Sologuren I et al (2014) Clinical features of Candidiasis in patients with inherited interleukin 12 receptor beta1 deficiency. Clin Infect Dis 58(2):204–213. doi:10.1093/cid/cit722

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Lanternier F, Pathan S, Vincent QB, Liu L, Cypowyj S, Prando C et al (2013) Deep dermatophytosis and inherited CARD9 deficiency. N Engl J Med 369(18):1704–1714. doi:10.1056/NEJMoa1208487

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Drewniak A, Gazendam RP, Tool AT, van Houdt M, Jansen MH, van Hamme JL et al (2013) Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood 121(13):2385–2392. doi:10.1182/blood-2012-08-450551

    CAS  PubMed  Google Scholar 

  47. Bochud PY, Chien JW, Marr KA, Leisenring WM, Upton A, Janer M et al (2008) Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med 359(17):1766–1777. doi:10.1056/NEJMoa0802629

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Koldehoff M, Beelen DW, Elmaagacli AH (2013) Increased susceptibility for aspergillosis and post-transplant immune deficiency in patients with gene variants of TLR4 after stem cell transplantation. Transpl Infect Dis: Off J Transpl Soc 15(5):533–539. doi:10.1111/tid.12115

    CAS  Google Scholar 

  49. Kesh S, Mensah NY, Peterlongo P, Jaffe D, Hsu K, Van den Brink M 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. doi:10.1196/annals.1358.012

    CAS  PubMed  Google Scholar 

  50. Carvalho A, Cunha C, Carotti A, Aloisi T, Guarrera O, Di Ianni M et al (2009) Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation. Exp Hematol 37(9):1022–1029. doi:10.1016/j.exphem.2009.06.004

    CAS  PubMed  Google Scholar 

  51. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M et al (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25(2):187–191. doi:10.1038/76048

    CAS  PubMed  Google Scholar 

  52. van der Graaf C, Kullberg BJ, Joosten L, Verver-Jansen T, Jacobs L, Van der Meer JW et al (2005) Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism. Cytokine 30(5):264–268. doi:10.1016/j.cyto.2005.02.001

    PubMed  Google Scholar 

  53. Carvalho A, De Luca A, Bozza S, Cunha C, D’Angelo C, Moretti S et al (2012) TLR3 essentially promotes protective class I-restricted memory CD8(+) T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients. Blood 119(4):967–977. doi:10.1182/blood-2011-06-362582

    CAS  PubMed  Google Scholar 

  54. Grube M, Loeffler J, Mezger M, Kruger B, Echtenacher B, Hoffmann P et al (2013) TLR5 stop codon polymorphism is associated with invasive aspergillosis after allogeneic stem cell transplantation. Med Mycol 51(8):818–825. doi:10.3109/13693786.2013.809630

    CAS  PubMed  Google Scholar 

  55. Rubino I, Coste A, Le Roy D, Roger T, Jaton K, Boeckh M et al (2012) Species-specific recognition of Aspergillus fumigatus by Toll-like receptor 1 and Toll-like receptor 6. J Infect Dis 205(6):944–954. doi:10.1093/infdis/jir882

    CAS  PubMed  Google Scholar 

  56. Cunha C, Di Ianni M, Bozza S, Giovannini G, Zagarella S, Zelante T 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(24):5394–5402. doi:10.1182/blood-2010-04-279307

    CAS  PubMed  Google Scholar 

  57. Chai LY, de Boer MG, van der Velden WJ, Plantinga TS, van Spriel AB, Jacobs C et al (2011) The Y238X stop codon polymorphism in the human beta-glucan receptor dectin-1 and susceptibility to invasive aspergillosis. J Infect Dis 203(5):736–743. doi:10.1093/infdis/jiq102

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Sainz J, Lupianez CB, Segura-Catena J, Vazquez L, Rios R, Oyonarte S et al (2012) Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary aspergillosis infection. PLoS One 7(2):e32273. doi:10.1371/journal.pone.0032273

    PubMed Central  CAS  PubMed  Google Scholar 

  59. Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M et al (2014) Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N Engl J Med 370(5):421–432. doi:10.1056/NEJMoa1211161

    CAS  PubMed  Google Scholar 

  60. Wójtowicz A, Lecompte T, Bibert S, Manuel O, Berger C, Boggian K et al (2014) PTX3 Polymorphisms are a major risk factor for invasive mold infection in solid organ transplantant recipients. ICAAC 2014 Meeting, September 2014, Washington, DC

  61. Granell M, Urbano-Ispizua A, Suarez B, Rovira M, Fernandez-Aviles F, Martinez C et al (2006) Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation. Exp Hematol 34(10):1435–1441. doi:10.1016/j.exphem.2006.06.005

    CAS  PubMed  Google Scholar 

  62. Sainz J, Hassan L, Perez E, Romero A, Moratalla A, Lopez-Fernandez E et al (2007) Interleukin-10 promoter polymorphism as risk factor to develop invasive pulmonary aspergillosis. Immunol Lett 109(1):76–82. doi:10.1016/j.imlet.2007.01.005

    CAS  PubMed  Google Scholar 

  63. Sainz J, Perez E, Gomez-Lopera S, Jurado M (2008) IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level. J Clin Immunol 28(5):473–485. doi:10.1007/s10875-008-9197-0

    CAS  PubMed  Google Scholar 

  64. Mezger M, Steffens M, Beyer M, Manger C, Eberle J, Toliat MR et al (2008) Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 expression in monocyte-derived dendritic cells. Blood 111(2):534–536. doi:10.1182/blood-2007-05-090928

    CAS  PubMed  Google Scholar 

  65. Carvalho A, Cunha C, Di Ianni M, Pitzurra L, Aloisi T, Falzetti F et al (2010) Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation. Bone Marrow Transplant 45(11):1645–1652. doi:10.1038/bmt.2010.28

    CAS  PubMed  Google Scholar 

  66. Sainz J, Salas-Alvarado I, Lopez-Fernandez E, Olmedo C, Comino A, Garcia F et al (2010) TNFR1 mRNA expression level and TNFR1 gene polymorphisms are predictive markers for susceptibility to develop invasive pulmonary aspergillosis. Int J Immunopathol Pharmacol 23(2):423–436

    CAS  PubMed  Google Scholar 

  67. Sainz J, Perez E, Hassan L, Moratalla A, Romero A, Collado MD et al (2007) Variable number of tandem repeats of TNF receptor type 2 promoter as genetic biomarker of susceptibility to develop invasive pulmonary aspergillosis. Hum Immunol 68(1):41–50. doi:10.1016/j.humimm.2006.10.011

    CAS  PubMed  Google Scholar 

  68. Cunha C, Giovannini G, Pierini A, Bell AS, Sorci G, Riuzzi F et al (2011) Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients. PLoS One 6(11):e27962. doi:10.1371/journal.pone.0027962

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Zaas AK, Liao G, Chien JW, Weinberg C, Shore D, Giles SS et al (2008) Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genet 4(6):e1000101. doi:10.1371/journal.pgen.1000101

    PubMed Central  PubMed  Google Scholar 

  70. Van der Graaf CA, Netea MG, Morre SA, Den Heijer M, Verweij PE, Van der Meer JW, Kullberg BJ (2006) Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur Cytokine Netw 17:29–34

    PubMed  Google Scholar 

  71. Plantinga TSJM, Scott WK, van de Vosse E, Velez Edwards DR, Smith PB, Alexander BD, Yang JC, Kremer D, Laird GM, Oosting M, Joosten LA, van der Meer JW, van Dissel JT, Walsh TJ, Perfect JR, Kullberg BJ, Netea MG (2012) Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis 205(6):934–943

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Wojtowicz A, Tissot F, Lamoth F, Orasch C, Eggimann P, Siegemund M et al (2014) Polymorphisms in tumor necrosis factor-alpha increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*. Crit Care Med 42(4):e304–e308. doi:10.1097/CCM.0000000000000208

    CAS  PubMed  Google Scholar 

  73. Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Meer JW, Kullberg BJ (2002) The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infect Dis 185(10):1483–1489. doi:10.1086/340511

    CAS  PubMed  Google Scholar 

  74. Woehrle T, Du W, Goetz A, Hsu HY, Joos TO, Weiss M et al (2008) Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans. Cytokine 41(3):322–329. doi:10.1016/j.cyto.2007.12.006

    CAS  PubMed  Google Scholar 

  75. Plantinga TS, van der Velden WJ, Ferwerda B, van Spriel AB, Adema G, Feuth T et al (2009) Early stop polymorphism in human DECTIN-1 is associated with increased Candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis 49(5):724–732

    CAS  PubMed  Google Scholar 

  76. Rosentul DC, Plantinga TS, Oosting M, Scott WK, Velez Edwards DR, Smith PB et al (2011) Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis 204(7):1138–1145. doi:10.1093/infdis/jir458

    PubMed Central  CAS  PubMed  Google Scholar 

  77. Saijo S, Fujikado N, Furuta T, Chung SH, Kotaki H, Seki K et al (2007) Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 8(1):39–46. doi:10.1038/ni1425

    CAS  PubMed  Google Scholar 

  78. van Till WMP, de Boer M, Hart MH, Beld MG, Boermeester MA (2008) Mannose-binding lectin deficiency facilitates abdominal Candida infections in patients with secondary peritonitis. Clin Vaccine Immunol 15:65–70

    PubMed Central  PubMed  Google Scholar 

  79. Johnson MD, Plantinga TS, van de Vosse E, Velez Edwards DR, Smith PB, Alexander BD et al (2012) Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin Infect Dis Off Publ Infect Dis Soc Am 54(4):502–510. doi:10.1093/cid/cir827

    CAS  Google Scholar 

  80. Choi EH, Foster CB, Taylor JG, Erichsen HC, Chen RA, Walsh TJ et al (2003) Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J Infect Dis 187(7):1153–1156. doi:10.1086/368345

    CAS  PubMed  Google Scholar 

  81. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J et al (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469(7330):419–423. doi:10.1038/nature09674

    CAS  PubMed  Google Scholar 

  82. Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA (2003) Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol 41(1):90–96

    PubMed Central  CAS  PubMed  Google Scholar 

  83. Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C et al (2013) Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun 4:1342. doi:10.1038/ncomms2343

    PubMed Central  PubMed  Google Scholar 

  84. Kumar V, Cheng SC, Johnson MD, Smeekens SP, Wojtowicz A, Giamarellos-Bourboulis E et al (2014) Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia. Nat Commun 5:4675. doi:10.1038/ncomms5675

    CAS  PubMed  Google Scholar 

  85. Glocker EO, Hennigs A, Nabavi M, Schaffer AA, Woellner C, Salzer U et al (2009) A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 361(18):1727–1735

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ et al (2009) Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med 361(21):2046–2055. doi:10.1056/NEJMoa0905506

    PubMed Central  CAS  PubMed  Google Scholar 

  87. Picard C, Casanova JL, Puel A (2011) Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkappaBalpha deficiency. Clin Microbiol Rev 24(3):490–497. doi:10.1128/CMR. 00001-11

    PubMed Central  CAS  PubMed  Google Scholar 

  88. Schimke LF, Rieber N, Rylaarsdam S, Cabral-Marques O, Hubbard N, Puel A et al (2013) A novel gain-of-function IKBA mutation underlies ectodermal dysplasia with immunodeficiency and polyendocrinopathy. J Clin Immunol 33(6):1088–1099. doi:10.1007/s10875-013-9906-1

    CAS  PubMed  Google Scholar 

  89. Morgan NV, Goddard S, Cardno TS, McDonald D, Rahman F, Barge D et al (2011) Mutation in the TCRalpha subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRalphabeta+ T cells. J Clin Investig 121(2):695–702. doi:10.1172/JCI41931

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B et al (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441(7090):179–185. doi:10.1038/nature04702

    CAS  PubMed  Google Scholar 

  91. Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schaffer AA et al (2012) The phenotype of human STK4 deficiency. Blood 119(15):3450–3457. doi:10.1182/blood-2011-09-378158

    PubMed Central  CAS  PubMed  Google Scholar 

  92. Nehme NT, Pachlopnik Schmid J, Debeurme F, Andre-Schmutz I, Lim A, Nitschke P et al (2012) MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival. Blood 119(15):3458–3468. doi:10.1182/blood-2011-09-378364

    CAS  PubMed  Google Scholar 

  93. Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JW (2007) CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol 119(2):482–487. doi:10.1016/j.jaci.2006.10.007

    CAS  PubMed  Google Scholar 

  94. Ouederni M, Vincent QB, Frange P, Touzot F, Scerra S, Bejaoui M et al (2011) Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. Blood 118(19):5108–5118. doi:10.1182/blood-2011-05-352716

    CAS  PubMed  Google Scholar 

  95. Gorska MM, Alam R (2012) A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia. Blood 119(6):1399–1406. doi:10.1182/blood-2011-04-350686

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC et al (2011) Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature 475(7357):471–476. doi:10.1038/nature10246

    PubMed Central  CAS  PubMed  Google Scholar 

  97. Kuijpers TW, Ijspeert H, van Leeuwen EM, Jansen MH, Hazenberg MD, Weijer KC et al (2011) Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations. Blood 117(22):5892–5896. doi:10.1182/blood-2011-01-329052

    CAS  PubMed  Google Scholar 

  98. Puck JM (2011) Neonatal screening for severe combined immunodeficiency. Curr Opin Pediatr 23(6):667–673. doi:10.1097/MOP.0b013e32834cb9b0

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L et al (2012) Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine 91(4):e1–e19. doi:10.1097/MD.0b013e31825f95b9

    PubMed Central  CAS  PubMed  Google Scholar 

  100. Woellner C, Gertz EM, Schaffer AA, Lagos M, Perro M, Glocker EO et al (2010) Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. J Allergy Clin Immunol 125(2):424–32 e8. doi:10.1016/j.jaci.2009.10.059

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Engelhardt KR, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G et al (2009) Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol 124(6):1289–302 e4. doi:10.1016/j.jaci.2009.10.038

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV et al (2010) Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med 207(2):299–308. doi:10.1084/jem.20091669

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Sarkadi AK, Tasko S, Csorba G, Toth B, Erdos M, Marodi L (2014) Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients. J Clin Immunol 34(2):181–193. doi:10.1007/s10875-014-9987-5

    CAS  PubMed  Google Scholar 

  104. Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S et al (2006) Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25(5):745–755. doi:10.1016/j.immuni.2006.09.009

    CAS  PubMed  Google Scholar 

  105. de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M et al (2008) Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med 205(7):1543–1550. doi:10.1084/jem.20080321

    PubMed Central  PubMed  Google Scholar 

  106. Prando C, Samarina A, Bustamante J, Boisson-Dupuis S, Cobat A, Picard C et al (2013) Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds. Medicine 92(2):109–122. doi:10.1097/MD.0b013e31828a01f9

    CAS  PubMed  Google Scholar 

  107. Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK et al (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332(6025):65–68. doi:10.1126/science.1200439

    PubMed Central  CAS  PubMed  Google Scholar 

  108. Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A et al (2011) Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med 208(8):1635–1648. doi:10.1084/jem.20110958

    PubMed Central  CAS  PubMed  Google Scholar 

  109. van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C et al (2011) STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med 365(1):54–61. doi:10.1056/NEJMoa1100102

    PubMed  Google Scholar 

  110. Boisson B, Wang C, Pedergnana V, Wu L, Cypowyj S, Rybojad M et al (2013) An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity 39(4):676–686. doi:10.1016/j.immuni.2013.09.002

    CAS  PubMed  Google Scholar 

  111. Seo KW, Kim DH, Sohn SK, Lee NY, Chang HH, Kim SW et al (2005) Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation. Bone Marrow Transplant 36(12):1089–1095. doi:10.1038/sj.bmt.1705181

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by the Swiss National Foundation (Grand number 324730-144054), the Leenaards Foundation, the Santos-Suarez Foundation, the Loterie Romande, Mérieux Research Grant (MRG), the FLTO Foundation (Fondation Lausannoise pour la transplantation d’organes) and the European Union’s Seventh Framework Program (FP7/2007-2013) under grant agreement n° HEALTH-2010-260338 (ALLFUN).

Author information

Authors and Affiliations

  1. Infectious Disease Service, Department of Medicine, Lausanne University Hospital (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland

    Agnieszka Wójtowicz & Pierre-Yves Bochud

Authors
  1. Agnieszka Wójtowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierre-Yves Bochud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre-Yves Bochud.

Additional information

This article is a contribution to the special issue on Immunopathology of Fungal Diseases - Guest Editor: Jean-Paul Latge

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wójtowicz, A., Bochud, PY. Host genetics of invasive Aspergillus and Candida infections. Semin Immunopathol 37, 173–186 (2015). https://doi.org/10.1007/s00281-014-0468-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-014-0468-y

Keywords

Search

Navigation