Optimizing outcomes in immunocompromised hosts: Understanding the role of immunotherapy in invasive fungal diseases

Frontiers in Microbiology

Volumn 6, Issue NOV, 2015, Pages

  Ravikumar, Sharada ^a,b   Win, Mar Soe ^a,b   Chai, Louis Yi Ann ^a,b  

^a NATIONAL UNIVERSITY HEALTH SYSTEM   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Cytokines; Immune enhancement; Immune regulation; Immunocompromised; Invasive fungal infections

Indexed keywords

ANTIGEN RECOGNITION; CELL THERAPY; CELL TRANSFER; CLINICAL TRIAL (TOPIC); CROSS REACTION; FUNGAL VIRULENCE; GRANULOCYTE TRANSFUSION; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPROMISED PATIENT; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; IMMUNOTHERAPY; MYCOSIS; NATURAL KILLER CELL; NONHUMAN; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; VACCINATION;

EID: 84949740234     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2015.01322     Document Type: Review

References (111)

1. Bandera, A., Trabattoni, D., Ferrario, G., Cesari, M., Franzetti, F., Clerici, M., et al. (2008). Interferon-gamma and granulocyte-macrophage colony stimulating factor therapy in three patients with pulmonary aspergillosis. Infection 36, 368-373. doi: 10.1007/s15010-008-7378-7
2. Becker, K. L., Ifrim, D. C., Quintin, J., Netea, M. G., and van de Veerdonk, F. L. (2015). Antifungal innate immunity: recognition and inflammatory networks. Semin. Imunopathol. 37, 107-116. doi: 10.1007/s00281-014-0467-z
3. Bellocchio, S., Montagnoli, C., Bozza, S., Gaziano, R., Rossi, G., Mambula, S. S., et al. (2004). The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 172, 3059-3069. doi: 10.4049/jimmunol.172.5.3059
4. Blumberg, H. M., Jarvis, W. R., Soucie, J. M., Edwards, J. E., Patterson, J. E., Pfaller, M. A., et al. (2001). Risk factors for Candida bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis survey. Clin. Infect. Dis. 33, 177-186. doi: 10.1086/321811
5. Bochud, P. Y., Chien, J. W., Marr, K. A., Leisenring, W. M., Upton, A., Janer, M., et al. (2008). Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 359, 1766-1777. doi: 10.1056/NEJMoa0802629
6. Bourgeois, C., and Kuchler, K. (2012). Fungal pathogens-a sweet and sour treat for Toll-like receptors. Front. Cell Infect. Microbiol. 2:142. doi: 10.3389/fcimb.2012.00142
7. Bouzani, M., Ok, M., McCormick, A., Ebel, F., Kurzai, O., Morton, C. O., et al. (2011). Human NK cells display important antifungal activity against Aspergillus fumigatus, which is directly mediated by IFN-γ release. J. Immunol. 187, 1369-1376. doi: 10.4049/jimmunol.1003593
8. Bozza, S., Clavaud, C., Giovannini, G., Fontaine, T., Beauvais, A., Sarfati, J., et al. (2009). Immune sensing of Aspergillus fumigatus proteins, glycolipids, and polysaccharides and the impact on Th immunity and vaccination. J. Immunol. 183, 2407-2414. doi: 10.4049/jimmunol.0900961
9. Bozza, S., Gaziano, R., Lipford, G. B., Montagnoli, C., Bacci, A., Di Francesco, P., et al. (2002). Vaccination of mice against invasive aspergillosis with recombinant Aspergillus proteins and CpG oligodeoxynucleotides as adjuvants. Microbes Infect. 4, 1281-1290. doi: 10.1016/S1286-4579(02)00007-2
10. Bozza, S., Perruccio, K., Montagnoli, C., Gaziano, R., Bellocchio, S., Burchielli, E., et al. (2003). A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102, 3807-3814. doi: 10.1182/blood-2003-03-0748
11. Braem, S. G., Rooijakkers, S. H., van Kessel, K. P., de Cock, H., Wosten, H. A., van Strijp, J. A., et al. (2015). Effective neutrophil phagocytosis of Aspergillus fumigatus is mediated by classical pathway complement activation. J. Innate Immun. 7, 364-374. doi: 10.1159/000369493
12. Brown, G. D., Denning, D. W., Gow, N. A., Levitz, S. M., Netea, M. G., and White, T. C. (2012). Hidden killers: human fungal infections. Sci. Transl. Med. 4, 165rv13. doi: 10.1126/scitranslmed.3004404
13. Bryan, R. A., Guimaraes, A. J., Hopcraft, S., Jiang, Z., Bonilla, K., Morgenstern, A., et al. (2012). Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens. Mycopathologia 173, 463-471. doi: 10.1007/s11046-011-9476-9
14. Bryan, R. A., Jiang, Z., Howell, R. C., Morgenstern, A., Brushertseifer, F., Casadevall, A., et al. (2010). Radioimmunotherapy is more effective than antifungal treatment in experimental cryptococcal infection. J. Infect. Dis. 202, 633-637. doi: 10.1086/654813
15. Carvalho, A., Pasqualotto, A. C., Pitzurra, L., Romani, L., Denning, D. W., and Rodrigues, F. (2008). Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J. Infect. Dis. 197, 618-621. doi: 10.1086/526500
16. Cenci, E., Mencacci, A., Spreca, A., Montagnoli, C., Bacci, A., Perruccio, K., et al. (2002). Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation. Infect. Immun. 70, 2375-2382. doi: 10.1128/IAI.70.5.2375-2382.2002
17. Chai, L. Y., Vonk, A. G., Kullberg, B. J., and Netea, M. G. (2011). Immune response to Aspergillus fumigatus in compromised hosts: from bedside to bench. Future Microbiol. 6, 73-83. doi: 10.2217/fmb.10.158
18. Chaturvedi, A. K., Kavishwar, A., Shiva Keshava, G. B., and Shukla, P. K. (2005). Monoclonal immunoglobulin G1 directed against Aspergillus fumigatus cell wall glycoprotein protects against experimental murine aspergillosis. Clin. Diagn. Lab. Immunol. 12, 1063-1068. doi: 10.1128/cdli.12.9.1063-1068.2005
19. Cheng, S. C., van de Veerdonk, F., Smeekens, S., Joosten, L. A., van der Meer, J. W., Kullberg, B. J., et al. (2010). Candida albicans dampens host defense by downregulating IL-17 production. J. Immunol. 185, 2450-2457. doi: 10.4049/jimmunol.1000756
20. Cunha, C., Aversa, F., Lacerda, J. F., Busca, A., Kurzai, O., Grube, M., et al. (2014). Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 370, 421-432. doi: 10.1056/NEJMoa1211161
21. Delsing, C., Gresnigt, M., Leentjens, J., Preijers, F., Allantaz, Frager, F., Kox, M., et al. (2014). Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infect. Dis. 14:166. doi: 10.1186/1471-2334-14-166
22. de Pauw, B. E., and Picazo, J. J. (2008). Present situation in the treatment of invasive fungal infections. Int. J. Antimicrob. Agents 32, 167-171. doi: 10.1016/S0924-8579(08)70020-7
23. + T cells mediate the protective effect of the recombinant Aspf3-based anti-aspergillosis vaccine. Infect. Immun. 79, 2257-2266. doi: 10.1128/IAI.01311-10
24. Dignani, M. C., Anaissie, E. J., Hester, J. P., O'Brien, S., Vartivarian, S. E., Rex, J. H., et al. (1997). Treatment of neutropenia-related fungal infections with granulocyte colony-stimulating factor-elicited white blood cell transfusions: a pilot study. Leukemia 11, 1621-1630. doi: 10.1038/sj.leu.2400811
25. Drewniak, A., Gazendam, R. P., Tool, A. T., van Houdt, M., Jansen, M. H., van Hamme, J. L., et al. (2013). Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood 121, 2385-2392. doi: 10.1182/blood-2012-08-450551
26. Dromer, F., Charreire, J., Contrepois, A., Carbon, C., and Yeni, P. (1987). Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect. Immun. 55, 749-752.
27. Erjavec, Z., Kluin-Nelemans, H., and Verwejj, P. E. (2009). Trends in invasive fungal infections, with emphasis on invasive aspergillosis. Clin. Microbiol. Infect. 15, 625-633. doi: 10.1111/j.1469-0691.2009.02929.x
28. Esteban, A., Popp, M. W., Vyas, V. K., Strijbis, K., Ploegh, H. L., and Fink, G. R. (2011). Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages. Proc. Natl. Acad. Sci. U.S.A. 108, 14270-14275. doi: 10.1073/pnas.1111415108
29. Estrada, C., Desai, A. G., Chirch, L. M., Suh, H., Seidman, R., Darras, F., et al. (2012). Invasive aspergillosis in a renal transplant recipient successfully treated with interferon-gamma. Case Rep. Transplant. 2012, 5. doi: 10.1155/2012/493758
30. Ferwerda, B., Ferwerda, G., Plantinga, T. S., Willment, J. A., van Spriel, A. B., Venselaar, H., et al. (2009). Human dectin-1 deficiency and mucocutaneous fungal infections. N. Engl. J. Med. 361, 1760-1767. doi: 10.1056/NEJMoa0901053
31. Goodridge, H., S., and Underhill, D. M. (2008). Fungal recognition by TLR2 and Dectin-1. Handb. Exp. Pharmaco. 183, 87-109. doi: 10.1007/978-3-540-72167-3_5
32. Glocker, E. O., Hennigs, A., Nabavi, M., Schaffer, A. A., Woellner, C., Salzer, U., et al. (2009). A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361, 1727-1735. doi: 10.1056/NEJMoa0810719
33. Gresnigt, M. S., Rosler, B., Jacobs, C. W., Becker, K. L., Joosten, L. A., van der Meer, J. W., et al. (2013). The IL-36 receptor pathway regulates Aspergillus fumigatus-induced Th1 and Th17 responses. Eur. J. Immunol. 43, 416-426. doi: 10.1002/eji.201242711
34. Gringhuis, S. I., Kaptein, T. M., Wevers, B. A., Theelen, B., van der Vlist, M., Boekhout, T., et al. (2012). Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a non-canonical caspase-8 inflammasome. Nat. Immunol. 13, 246-254. doi: 10.1038/ni.2222
35. Gross, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschlager, N., Endres, S., et al. (2009). Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459, 433-436. doi: 10.1038/nature07965
36. Hamad, M. (2012). Innate and adaptive antifungal immune responses: partners on an equal footing. Mycoses 55, 205-217. doi: 10.1111/j.1439-0507.2011.02078.x
37. Han, Y., and Cutler, J. E. (1995). Antibody response that protects against disseminated candidiasis. Infect. Immun. 63, 2714-2719.
38. Herbrecht, R., Denning, D. W., Patterson, T. F., Bennett, J. E., Greene, R. E., Oestmann, J. W., et al. (2002). Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 347, 408-415. doi: 10.1056/NEJMoa020191
39. Herbrecht, R., Fohrer, C., and Nivoix, Y. (2006). Mycograb for the treatment of invasive candidiasis. Clin. Infect. Dis. 43, 1083-1084. doi: 10.1086/507547
40. Hodgetts, S., Nooney, L., Al-Akeel, R., Curry, A., Awad, S., Matthews, R., et al. (2008). Efungumab and caspofungin: pre-clinical data supporting synergy. J. Antimicrob. Chemother. 61, 1132-1139. doi: 10.1093/jac/dkn075
41. Illerhaus, G., Wirth, K., Dwenger, A., Waller, C. F., Garbe, A., Brass, V., et al. (2002). Treatment and prophylaxis of severe infections in neutropenic patients by granulocyte transfusions. Ann. Hematol. 81, 273-281. doi: 10.1007/s00277-002-0439-6
42. Ito, J. I., Lyons, J. M., Hong, T. B., Tamae, D., Liu, Y. K., Wilczynski, S. P., et al. (2006). Vaccinations with recombinant variants of Aspergillus fumigatus allergen Aspf3 protect mice against invasive aspergillosis. Infect. Immun. 74, 5075-5084. doi: 10.1128/IAI.00815-06
43. Kawai, T., and Akira, S. (2011). Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650. doi: 10.1016/j.immuni.2011.05.006
44. Kelleher, P., Goodsall, A., Mulgirigama, A., Kunst, H., Henderson, D. C., Wilson, R., et al. (2006). Interferon-gamma therapy in two patients with progressive chronic pulmonary aspergillosis. Eur. Respir. J. 27, 1307-1310. doi: 10.1183/09031936.06.00021705
45. Kesh, S., Mensah, N. Y., Peterlongo, P., Jaffe, D., Hsu, K., Van Den Brink, M., et al. (2005). TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive apergillosis after allogeneic stem cell transplantation. Ann. N. Y. Acad. Sci. 1062, 95-103. doi: 10.1196/annals.1358.012
46. Ketelut-Carneiro, N., Silva, G. K., Rocha, F. A., Milanezi, C. M., Cavalcanti-Neto, F. F., Zamboni, D. S., et al. (2015). IL-18 triggered by the Nlrp3 inflammasome induces host innate resistance in a pulmonary model of fungal infection. J. Immunol. 194, 4507-4517. doi: 10.4049/jimmunol.1402321
47. Kohler, J. R., Casadevall, A., and Perfect, J. (2015). The spectrum of fungi that infects humans. Cold Spring Harb. Perspect. Med. 5:a019273. doi: 10.1101/cshperspect.a019273
48. Kuhara, T., Uchida, K., and Yamaguchi, H. (2000). Therapeutic efficacy of human macrophage colony-stimulating factor, used alone and in combination with antifungal agents, in mice with systemic Candida albicans infection. Antimicrob. Agents Chemother. 44, 19-23. doi: 10.1128/AAC.44.1.19-23.2000
49. Larsen, R. A., Pappas, P. G., Perfect, J., Aberg, J. A., Casadevall, A., Cloud, G. A., et al. (2005). Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob. Agents Chemother. 49, 952-958. doi: 10.1128/AAC.49.3.952-958.2005
50. Loures, F. V., Pina, A., Felonato, M., Araujo, E. F., Leite, K. R., and Calich, V. L. (2010). Toll-like receptor 4 signaling leads to severe fungal infection associated with enhanced proinflammatory immunity and impaired expansion of regulatory T cells. Infect. Immun. 78, 1078-1088. doi: 10.1128/IAI.01198-09
51. Mantovani, A., Cassatella, M. A., Costantini, C., and Jaillon, S. (2011). Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 11, 519-531. doi: 10.1038/nri3024
52. Marr, K. A., Carter, R. A., Boeckh, M., Martin, P., and Corey, L. (2002). Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100, 4358-4366. doi: 10.1182/blood-2002-05-1496
53. Matthews, R. C., Rigg, G., Hodgetts, S., Carter, T., Chapman, C., Gregory, C., et al. (2003). Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob. Agents Chemother. 47, 2208-2216. doi: 10.1128/AAC.47.7.2208-2216.2003
54. Mehrad, B., Strieter, R. M., and Standiford, T. J. (1999). Role of TNF-alpha in pulmonary host defense in murine invasive aspergillosis. J. Immunol. 162, 1633-1640.
55. Mezger, M., Kneitz, S., Wozniok, I., Kurzai, O., Einsele, H., and Loeffler, J. (2008). Proinflammatory response of immature human dendritic cells is mediated by dectin-1 after exposure to Aspergillus fumigatus germ tubes. J. Infect. Dis. 197, 924-931. doi: 10.1086/528694
56. Mezger, M., Einsele, H., and Loeffler, J. (2010). Genetic susceptibility to infections with Aspergillus fumigatus. Crit. Rev. Microbiol. 36, 168-177. doi: 10.3109/10408410903530619
57. Moragues, M. D., Omaetxebarria, M. J., Elguezabal, N., Sevilla, M. J., Conti, S., Polonelli, L., et al. (2003). A monoclonal antibody directed against a Candida albicans cell wall mannoprotein exerts three anti-C. albicans activities. Infect. Immun. 71, 5273-5279. doi: 10.1128/IAI.71.9.5273-5279.2003
58. Morrison, B. E., Park, S. J., Mooney, J. M., and Mehrad, B. (2003). Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis. J. Clin. Invest. 112, 1862-1870. doi: 10.1172/JCI18125
59. Mousset, S., Hermann, S., Klein, S. A., Bialleck, H., Duchscherer, M., Bomke, B., et al. (2005). Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia. Ann. Hematol. 84, 734-741. doi: 10.1007/s00277-005-1055-z
60. Mueller-Loebnitz, C., Ostermann, H., Franzke, A., Loeffler, J., Uharek, L., Topp, M., et al. (2013). Immunological aspects of Candida and Aspergillus systemic fungal infections. Interdiscip. Perspect. Infect. Dis. 2013, 102934. doi: 10.1155/2013/102934
61. Nemunaitis, J., Shannon-Dorcy, K., Appelbaum, F. R., Meyers, J., Owens, A., Day, R., et al. (1993). Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony-stimulating factor. Blood 82, 1422-1427.
62. 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, 265-273. doi: 10.1086/595846
63. Netea, M. G., Brown, G. D., Kullberg, B. J., and Gow, N. A. (2008). An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol. 6, 67-78. doi: 10.1038/nrmicro1815
64. Netea, M. G., Gow, N. A., Munro, C. A., 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. Invest. 116, 1642-1650. doi: 10.1172/JCI27114
65. O'Brien, B. L., Parrent, J. L., Jackson, J. A., Moncalvo, J. M., and Vilgalys, R. (2005). Fungal community analysis by large-scale sequencing of environmental samples. Appl. Environ. Microbiol. 71, 5544-5550. doi: 10.1128/AEM.71.9.5544-5550.2005
66. Pachl, J., Svoboda, P., Jacobs, F., Vandewoude, K., van der Hoven, B., Spronk, P., et al. (2006). A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination withan antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin. Infect. Dis. 42, 1404-1413. doi: 10.1086/503428
67. Park, S. J., Hughes, M. A., Burdick, M., Streiter, R. M., and Mehrad, B. (2009). Early NK cell-derived IFN-gamma is essential to host defense in neutropenic invasive aspergillosis. J. Immunol. 182, 4306-4312. doi: 10.4049/jimmunol.0803462
68. Pasare, C., and Medzhitov, R. (2005). Toll-like receptors: linking innate and adaptive immunity. Adv. Exp. Med. Biol. 560, 11-18. doi: 10.1007/0-387-24180-9_2
69. Perlin, D. S. (2007). Resistance to echinocandin-class antifungal drugs. Drug Resist. Updat 10, 121-130. doi: 10.1016/j.drup.2007.04.002
70. Perruccio, K., Bozza, S., Montagnoli, C., Bellocchio, S., Aversa, F., Martelli, M., et al. (2004). Prospects for dendritic cell vaccination against fungal infections in hematopoietic transplantation. Blood Cells Mol. Dis. 33, 248-255. doi: 10.1016/j.bcmd.2004.08.011
71. Pikman, R., and Ben-Ami, R. (2012). Immune modulators as adjuncts for the prevention and treatment of invasive fungal infections. Immunotherapy 4, 1869-1882. doi: 10.2217/imt.12.127
72. Plantinga, T. S., van der Velden, W. J., Ferwerda, B., van Spriel, A. B., 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, 724-732. doi: 10.1086/604714
73. Price, T. H., Bowden, R. A., Boeckh, M., Bux, J., Nelson, K., Liles, W. C., et al. (2000). Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation. Blood 95, 3302-3309.
74. Roden, M. M., Zaoutis, T. E., Buchanan, W. L., Knudsen, T. A., Sarkisova, T. A., Schaufele, R. L., et al. (2005). Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin. Infect. Dis. 41, 634-653. doi: 10.1086/432579
75. Rodrigues, M. E., Silva, S., Azeredo, J., and Henriques, M. (2014). Novel strategies to fight Candida species infection. Crit. Rev. Microbiol 10, 1-13. doi: 10.3109/1040841X.2014.974500
76. Roilides, E., Tsaparidou, S., Kadiltsoglou, I., Sein, T., and Walsh, T. J. (1999). Interleukin-12 enhances antifungal activity of human mononuclear phagocytes against Aspergillus fumigatus: implications for a gamma interferon-independent pathway. Infect. Immun. 67, 3047-3050.
77. Romani, L. (2011). Immunity to fungal infections. Nat. Rev. Immunol. 11, 275-288. doi: 10.1038/nri2939
78. Romani, L., and Puccetti, P. (2008). Immune regulation and tolerance to fungi in the lungs and skin. Chem. Immunol. Allergy 94, 124-137. doi: 10.1159/000154957
79. Romani, L., Puccetti, P., and Bistoni, F. (1997). Interleukin-12 in infectious diseases. Clin. Microbiol. Rev. 10, 611-636.
80. Safdar, A., Rodriguez, G. H., Lichtiger, B., Dickey, B. F., Kontoyiannis, D. P., Freireich, E. J., et al. (2006). Recombinant interferon gamma-1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions. Cancer 106, 2664-2671. doi: 10.1002/cncr.21929
81. Safdar, A., Rodriguez, G., Zuniga, J., Akhrass, F., Georgescu, G., and Pande, A. (2013). Granulocyte macrophage colony-stimulating factor in 66 patients with myeloid or lymphoid neoplasms and recipients of hematopoietic stem cell transplantation with invasive fungal disease. Acta Heamatol. 129, 26-34. doi: 10.1159/000342121
82. Said-Sadier, N., Padilla, E., Langsley, G., and Ojcius, D. M. (2010). Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS ONE 5:e10008. doi: 10.1371/journal.pone.0010008
83. Saijo, S., Ikeda, S., Yamabe, K., Kakuta, S., Ishigame, H., Akitsu, A., et al. (2010). Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32, 681-691. doi: 10.1016/j.immuni.2010.05.001
84. Schmidt, S., Tramsen, L., Hanisch, M., Latge, J. P., Huenecke, S., Koehl, U., et al. (2011). Human natural killer cells exhibit direct activity against Aspergillus fumigatus hyphae, but not against resting conidia. J. Infect. Dis. 203, 430-435. doi: 10.1093/infdis/jiq062
85. Seidel, M. G., Peters, C., Wacker, A., Northoff, H., Moog, R., Boehme, A., et al. (2008). Randomized phase III study of granulocyte transfusions in neutropenic patients. Bone Marrow Transplant. 42, 679-684. doi: 10.1038/bmt.2008.237
86. Shao, C., Qu, J., He, L., Zhang, Y., Wang, J., Zhou, H., et al. (2005). Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis. Genes Immun. 6, 103-114. doi: 10.1038/sj.gene.6364167
87. Slavin, M. A., Kannan, K., Buchanan, M. R., Sasadeusz, J., and Roberts, A. W. (2002). Successful allogeneic stem cell transplant after invasive pulmonary zygomycosis. Leuk. Lymphoma 43, 437-439. doi: 10.1080/10428190290006305
88. Smith, T. J., Khatcheressian, J., Lyman, G. H., Ozer, H., Armitage, J. O., Balducci, L., et al. (2006). 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J. Clin. Oncol. 24, 3187-3205. doi: 10.1200/JCO.2006.06.4451
89. Spellberg, B. (2011). Vaccines for invasive fungal infections. F1000 Med. Rep. 3, 13. doi: 10.3410/M3-13
90. Stevens, D. A. (2004). Vaccinate against aspergillosis! A call to arms of the immune system. Clin. Infect. Dis. 38, 1131-1136. doi: 10.1086/382882
91. Stevens, D. A., Clemons, K. V., and Liu, M. (2011). Developing a vaccine against aspergillosis. Med. Mycol. 49(Suppl. 1), S170-S176. doi: 10.3109/13693786.2010.497775
92. Stuehler, C., Khanna, N., Bozza, S., Zelante, T., Moretti, S., Kruhm, M., et al. (2011). Cross-protective Th1 immunity against Aspergillus fumigatus and Candida albicans. Blood 117, 5881-5891. doi: 10.1182/blood-2010-12-325084
93. Takeda, K., and Akira, S. (2005). Toll like receptors in innate immunity. Int. Immunol. 17, 1-14. doi: 10.1093/intimm/dxh186
94. Tessarolli, V., Gasparoto, T. H., Lima, H. R., Figueira, E. A., Garlet, T. P., Torres, S. A., et al. (2010). Absence of TLR2 influences survival of neutrophils after infection with Candida albicans. Med. Mycol. 48, 129-140. doi: 10.3109/13693780902964339
95. Ting, J. P., Duncan, J. A., and Lei, Y. (2010). How the inflammasome NLRs function in the innate immune system. Science 327, 286-290. doi: 10.1126/science.1184004
96. Toren, A., Or, R., Ackerstein, A., and Nagler, A. (1997). Invasive fungal infections in lymphoma patients receiving immunotherapy following autologous bone marrow transplantation (ABMT). Bone Marrow Transplant. 20, 67-69. doi: 10.1038/sj.bmt.1700847
97. Torosantucci, A., Chiani, P., Bromuro, C., De Bernardis, F., Palma, A. S., Liu, Y., et al. (2009). Protection by anti-beta-glucan antibodies is associated with restricted beta-1, 3 glucan binding specificity and inhibition of fungal growth and adherence. PLoS ONE 4:5392. doi: 10.1371/journal.pone.0005392
98. Uematsu, S., and Akira, S. (2008). Toll-like receptors (TLRs) and their ligands. Handb. Exp. Pharmacol. 183, 1-20. doi: 10.1007/978-3-540-72167-3_1
99. Van de Veerdonk, F. L., Netea, M. G., Joosten, L. A., van der Meer, J. W., and Kullberg, B. J. (2010). Novel strategies for the prevention and treatment of Candida infections: the potential of immunotherapy. FEMS Microbiol. Rev. 34, 1063-1075. doi: 10.1111/j.1574-6976.2010.00232.x
100. Vazquez, N., Walsh, T. J., Friedman, D., Chanock, S. J., and Lyman, C. A. (1998). Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans. Infect. Immun. 66, 145-150.
101. Verweij, P. E., Mellado, E., and Melchers, W. J. (2007). Multiple triazole resistant aspergillosis. N. Engl. J. Med. 356, 1481-1483. doi: 10.1056/NEJMc061720
102. Wey, S. B., Mori, M., Pfaller, M. A., Woolson, R. F., and Wenzel, R. P. (1989). Risk factors for hospital acquired candidemia. A matched case-control study. Arch. Intern. Med. 149, 2349-2353. doi: 10.1001/archinte.1989.00390100145030
103. Willment, J. A., Lin, H. H., Reid, D. M., Taylor, P. R., Williams, D. L., Wong, S. Y., et al. (2003). Dectin-1 expression and function are enhanced on alternatively activated and GM-CSF treated macrophages and are negatively regulated by IL-10, dexamethasone and lipopolysaccharide. J. Immunol. 171, 4569-4573. doi: 10.4049/jimmunol.171.9.4569
104. Winn, R. M., Gil-Lamaignere, C., Roilides, E., Simitsopoulou, M., Lyman, C. A., Maloukou, A., et al. (2003). Selective effects of interleukin (IL)-15 on antifungal activity and IL-8 release by polymorphonuclear leukocytes in response to hyphae of Aspergillus species. J. Infect. Dis. 188, 585-590. doi: 10.1086/377099
105. Wisplinghoff, H., Bischoff, T., Tallent, S. M., Seifert, H., Wenzel, R. P., and Edmond, M. B. (2004). Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39, 309-317. doi: 10.1086/421946
106. Wozniok, I., Hornbach, A., Schmitt, C., Frosch, M., Einsele, H., Hube, B., et al. (2008). Induction of ERK-kinase signaling triggers morphotype-specific killing of Candida albicans filaments by human neutrophils. Cell Microbiol. 10, 807-820. doi: 10.1111/j.1462-5822.2007.01086.x
107. Wuthrich, M., Gern, B., Hung, C. Y., Ersland, K., Rocco, N., Pick-Jacobs, J., et al. (2011). Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J. Clin. Invest. 121, 554-568. doi: 10.1172/JCI43984
108. Xie, J. L., Polvi, E. J., Shekhar-Guturja, T., and Cowen, L. E. (2014). Elucidating drug resistance in human fungal pathogens. Future Microbiol. 9, 523-542. doi: 10.2217/fmb.14.18
109. Xin, H., Dziadek, S., Bundle, D. R., and Cutler, J. E. (2008). Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce protection against candidiasis. Proc. Natl. Acad. Sci. U.S.A. 105, 13526-13531. doi: 10.1073/pnas.0803195105
110. Zelante, T., De Luca, A., D'Angelo, C., Moretti, S., and Romani, L. (2009). IL-17/Th17 in anti-fungal immunity: what's new? Eur. J. Immunol. 39, 645-648. doi: 10.1002/eji.200839102
111. + T cell-independent DNA vaccination against opportunistic infections. J. Clin. Invest. 115, 3536-3544. doi: 10.1172/JCI26306