Chapter 9 : Immunology of Invasive Candidiasis

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Invasive candidiasis is a life-threatening opportunistic infection and has emerged as a major cause of morbidity and mortality in critically ill patients. Until recently, was by far the predominant species, causing up to two-thirds of all cases of invasive candidiasis. This chapter highlights how the past several years have seen remarkable advances in understanding the basic cellular and immunological mechanisms underlying resistance to the fungus but also organ dysfunction and failure of recovery relating to invasive candidiasis. In experimental candidiasis, both defense mechanisms are activated through the delicate equilibrium between Th/Th17 cells and regulatory T cells (Tregs) limiting the consequences of the associated inflammatory pathology. The inflammatory response is initially mediated by cells of the innate immune system, followed by a later adaptive immune response, which is triggered by the signals originated by the innate immune system. The inflammatory response, initiated by cells of the innate immune system, is followed by adaptive immunity, which responds to, and at the same time regulates, signals emanating from the innate system. Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and limiting step in the kynurenine pathway of tryptophan catabolism. Our increasing understanding of the basic mechanisms that dictate development and function of Th17 cells, as well as our better knowledge of how Th17/Tregs regulate each other as well as other immune and nonimmune cells, provides guidelines for rational design of novel immunomodulatory therapies that limit inflammation in order to stimulate an effective immune response.

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9

Key Concept Ranking

Effector Th Cells
Innate Immune System
Immune Systems
Adaptive Immune System
Immune Receptors
Fungal Infections
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Image of FIGURE 1

Resistance and tolerance to . The figure illustrates how the interplay between resistance, i.e., the ability to limit pathogen burden, and tolerance, i.e., the ability of the host to defend itself by limiting the damage caused by the infection, determines the ability of the host to resist fungal exposure and infection. An increased understanding of the two mechanisms in infections could aid the diagnosis and treatment of candidiasis (see text for further insights). doi:10.1128/9781555817176.ch9.f1

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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Image of FIGURE 2

Major PRRs involved in recognition of and activation of subsequent inflammatory/Th responses. The exploitation of the IDO/Treg axis for regulatory mechanisms may have allowed the commensal to coevolve with the mammalian immune system and to survive in conditions of high-threat inflammation (see text for a detailed description). doi:10.1128/9781555817176.ch9.f2

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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IL-22 defines a novel immune pathway of antifungal resistance. DC-derived IL-23 promotes the production of IL-22 from cryptopatch CD3-NKp46 expressing RORγt, IL-23R, aryl hydrocarbon receptor, CCR5, and CCR7, indicating their similarity to gut RORγt NKp46 cells and cryptopatch lymphoid tissue inducer-like cells that are expanded by commensals. IL-22 targets epithelial cells for STAT3 activation and, together with IL-17A, for antimicrobial peptide production ( ). doi:10.1128/9781555817176.ch9.f3

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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1. Acosta-Rodriguez, E. V.,, L. Rivino,, J. Geginat,, D. Jarrossay,, M. Gattorno,, A. Lanzavecchia,, F. Sallusto, and, G. Napolitani. 2007. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 8:639646.
2. Ashman, R. B. 2008. Protective and pathologic immune responses against Candida albicans infection. Frontiers Biosci. 13:33343351.
3. Bellocchio, S.,, C. Montagnoli,, S. Bozza,, R. Gaziano,, G. Rossi,, S. S. Mambula,, A. Vecchi,, A. Mantovani,, S. M. Levitz, and, L. Romani. 2004. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 172:30593069.
4. Bonifazi, P.,, T. Zelante,, C. D’Angelo,, A. De Luca,, S. Moretti,, S. Bozza,, K. Perruccio,, R. G. Iannitti,, G. Giovannini,, C. Volpi,, F. Fallarino,, P. Puccetti, and, L. Romani. 2009. Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal Immunol. 2:362374.
5. Bourgeois, C.,, O. Majer,, I. E. Frohner,, I. Lesiak-Markowicz,, K. S. Hildering,, W. Glaser,, S. Stockinger,, T. Decker,, S. Akira,, M. Müller, and, K. Kuchler. 2011. Conventional dendritic cells mount a type I IFN response against Candida spp. requiring novel phagosomal TLR7-mediated IFN-β signaling. J. Immunol. 186:31043112.
6. Bourgeois, C.,, O. Majer,, I. E. Frohner,, L. Tierney, and, K. Kuchler. 2010. Fungal attacks on mammalian hosts: pathogen elimination requires sensing and tasting. Curr. Opin. Microbiol. 13:401408.
7. Brown, G. D. 2006. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 6:3343.
8. Cambi, A.,, M. G. Netea,, H. M. Mora-Montes,, N. A. Gow,, S. V. Hato,, D. W. Lowman,, B. J. Kullberg,, R. Torensma,, D. L. Williams, and, C. G. Figdor. 2008. Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. J. Biol. Chem. 283:2059020599.
9. Castagnola, E.,, and S. Buratti. 2009. Clinical aspects of invasive candidiasis in paediatric patients. Drugs 69(Suppl. 1):4550.
10. Chen, G.,, M. H. Shaw,, Y. G. Kim, and, G. Nunez. 2009. NOD-like receptors: role in innate immunity and inflammatory disease. Annu. Rev. Pathol. 4:365398.
11. Conti, H. R.,, F. Shen,, N. Nayyar,, E. Stocum,, J. N. Sun,, M. J. Lindemann,, A. W. Ho,, J. H. Hai,, J. J. Yu,, J. W. Jung,, S. G. Filler,, P. Masso-Welch,, M. Edgerton, and, S. L. Gaffen. 2009. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 206:299311.
12. Cooney, N. M.,, and B. S. Klein. 2008. Fungal adaptation to the mammalian host: it is a new world, after all. Curr. Opin. Microbiol. 11:511516.
13. De Luca, A.,, C. Montagnoli,, T. Zelante,, P. Bonifazi,, S. Bozza,, S. Moretti,, C. D’Angelo,, C. Vacca,, L. Boon,, F. Bistoni,, P. Puccetti,, F. Fallarino, and, L. Romani. 2007. Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J. Immunol. 179:59996008.
14. De Luca, A.,, T. Zelante,, C. D’Angelo,, S. Zagarella,, F. Fallarino,, A. Spreca,, R. G. Iannitti,, P. Bonifazi,, J. C. Renauld,, F. Bistoni,, P. Puccetti, and, L. Romani. 2010. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol. 3:361373.
15. Eyerich, K.,, S. Rombold,, S. Foerster,, H. Behrendt,, H. Hofmann,, J. Ring, and, C. Traidl-Hoffmann. 2007. Altered, but not diminished specific T cell response in chronic mucocutaneous candidiasis patients. Arch. Dermatol. Res. 299:475481.
16. Fenoglio, D.,, A. Poggi,, S. Catellani,, F. Battaglia,, A. Ferrera,, M. Setti,, G. Murdaca, and, M. R. Zocchi. 2009. Vδ1 T lymphocytes producing IFN-γ and IL-17 are expanded in HIV-1-infected patients and respond to Candida albicans. Blood 113:66116618.
17. Ferwerda, B.,, G. Ferwerda,, T. S. Plantinga,, J. A. Willment,, A. B. van Spriel,, H. Venselaar,, C. C. Elbers,, M. D. Johnson,, A. Cambi,, C. Huysamen,, L. Jacobs,, T. Jansen,, K. Verheijen,, L. Masthoff,, S. A. Morre,, G. Vriend,, D. L. Williams,, J. R. Perfect,, L. A. Joosten,, C. Wijmenga,, J. W. van der Meer,, G. J. Adema,, B. J. Kullberg,, G. D. Brown, and, M. G. Netea. 2009. Human dectin-1 deficiency and mucocutaneous fungal infections. N. Engl. J. Med. 361:17601767.
18. Filipe-Santos, O.,, J. Bustamante,, A. Chapgier,, G. Vogt,, L. de Beaucoudrey,, J. Feinberg,, E. Jouanguy,, S. Boisson-Dupuis,, C. Fieschi,, C. Picard, and, J. L. Casanova. 2006. Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin. Immunol. 18:347361.
19. Graham, L. M.,, and G. D. Brown. 2009. The Dectin-2 family of C-type lectins in immunity and homeostasis. Cytokine 48:148155.
20. Gringhuis, S. I.,, J. den Dunnen,, M. Litjens,, M. van der Vlist,, B. Wevers,, S. C. Bruijns, and, T. B. Geijtenbeek. 2009. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk. Nat. Immunol. 10:203213.
21. Grivennikov, S. I.,, F. R. Greten, and, M. Karin. Immunity, inflammation, and cancer. Cell 140:883899.
22. Grohmann, U.,, F. Fallarino, and, P. Puccetti. 2003. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol. 24:242248.
23. Gross, O.,, H. Poeck,, M. Bscheider,, C. Dostert,, N. Hannesschlager,, S. Endres,, G. Hartmann,, A. Tardivel,, E. Schweighoffer,, V. Tybulewicz,, A. Mocsai,, J. Tschopp, and, J. Ruland. 2009. Syk kinase signalling couples to the Nlrp3 inflammasome for antifungal host defence. Nature 459:433436.
24. Grossi, P. A. 2009. Clinical aspects of invasive candidiasis in solid organ transplant recipients. Drugs 69(Suppl. 1):1520.
25. Haas-Stapleton, E. J.,, Y. Lu,, S. Hong,, M. Arita,, S. Favoreto,, S. Nigam,, C. N. Serhan, and, N. Agabian. 2007. Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1. PLoS One 2:e1316.
26. Huang, W.,, L. Na,, P. L. Fidel, and, P. Schwarzenberger. 2004. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J. Infect. Dis. 190:624631.
27. Hube, B. 2009. Fungal adaptation to the host environment. Curr. Opin. Microbiol. 12:347349.
28. Joly, S.,, N. Ma,, J. J. Sadler,, D. R. Soll,, S. L. Cassel, and, F. S. Sutterwala. 2009. Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J. Immunol. 183:35783581.
29. Jouault, T.,, S. Ibata-Ombetta,, O. Takeuchi,, P. A. Trinel,, P. Sacchetti,, P. Lefebvre,, S. Akira, and, D. Poulain. 2003. Candida albicans phospholipomannan is sensed through Toll-like receptors. J. Infect. Dis. 188:165172.
30. Jouault, T.,, A. Sarazin,, M. Martinez-Esparza,, C. Fradin,, B. Sendid, and, D. Poulain. 2009. Host responses to a versatile commensal: PAMPs and PRRs interplay leading to tolerance or infection by Candida albicans. Cell. Microbiol. 11:10071015.
31. Kaufmann, S. H.,, and V. K. Kuchroo. 2009. Th17 cells. Microbes Infect. 11:579583.
32. Kohatsu, L.,, D. K. Hsu,, A. G. Jegalian,, F. T. Liu, and, L. G. Baum. 2006. Galectin-3 induces death of Candida species expressing specific beta-1,2-linked mannans. J. Immunol. 177:47184726.
33. Korn, T.,, E. Bettelli,, M. Oukka, and, V. K. Kuchroo. 2009. IL-17 and Th17 cells. Annu. Rev. Immunol. 27:485517.
34. Lee, S. J.,, N. Y. Zheng,, M. Clavijo, and, M. C. Nussenzweig. 2003. Normal host defense during systemic candidiasis in mannose receptor-deficient mice. Infect. Immun. 71:437445.
35. Legrand, F.,, M. Lecuit,, B. Dupont,, E. Bellaton,, M. Huerre,, P. S. Rohrlich, and, O. Lortholary. 2008. Adjuvant corticosteroid therapy for chronic disseminated candidiasis. Clin. Infect. Dis. 46:696702.
36. Leibundgut-Landmann, S.,, O. Gross,, M. J. Robinson,, F. Osorio,, E. C. Slack,, S. V. Tsoni,, E. Schweighoffer,, V. Tybulewicz,, G. D. Brown,, J. Ruland, and, E. S. C. Reis. 2007. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 8:630638.
37. Lilic, D. 2002. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr. Opin. Infect. Dis. 15:143147.
38. Lin, L.,, A. S. Ibrahim,, X. Xu,, J. M. Farber,, V. Avanesian,, B. Baquir,, Y. Fu,, S. W. French,, J. E. Edwards, Jr., and, B. Spellberg. 2009. Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog. 5:e1000703.
39. Littman, D. R.,, and A. Y. Rudensky. 2010. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 140:845858.
40. Liu, Y.,, B. Yang,, M. Zhou,, L. Li,, H. Zhou,, J. Zhang,, H. Chen, and, C. Wu. 2009. Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans. Eur. J. Immunol. 39:14721479.
41. Ma, C. S.,, G. Y. Chew,, N. Simpson,, A. Priyadarshi,, M. Wong,, B. Grimbacher,, D. A. Fulcher,, S. G. Tangye, and, M. C. Cook. 2008. Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J. Exp. Med. 205:15511557.
42. Martinon, F.,, and J. Tschopp. 2004. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117:561574.
43. Martinon, F.,, and J. Tschopp. 2005. NLRs join TLRs as innate sensors of pathogens. Trends Immunol. 26:447454.
44. Mean, M.,, O. Marchetti, and, T. Calandra. 2008. Bench-to-bedside review: Candida infections in the intensive care unit. Crit. Care 12:204.
45. Mellor, A. L.,, and D. H. Munn. 2004. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4:762774.
46. Milner, J. D.,, J. M. Brenchley,, A. Laurence,, A. F. Freeman,, B. J. Hill,, K. M. Elias,, Y. Kanno,, C. Spalding,, H. Z. Elloumi,, M. L. Paulson,, J. Davis,, A. Hsu,, A. I. Asher,, J. O’Shea,, S. M. Holland,, W. E. Paul, and, D. C. Douek. 2008. Impaired Th17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773776.
47. Miossec, P.,, T. Korn, and, V. K. Kuchroo. 2009. Inter-leukin-17 and type 17 helper T cells. N. Engl. J. Med. 361:888898.
48. Miyazato, A.,, K. Nakamura,, N. Yamamoto,, H. M. Mora-Montes,, M. Tanaka,, Y. Abe,, D. Tanno,, K. Inden,, X. Gang,, K. Ishii,, K. Takeda,, S. Akira,, S. Saijo,, Y. Iwakura,, Y. Adachi,, N. Ohno,, K. Mitsutake,, N. A. Gow,, M. Kaku, and, K. Kawakami. 2009. Toll-like receptor 9-dependent activation of myeloid dendritic cells by deoxynucleic acids from Candida albicans. Infect. Immun. 77:30563064.
49. Moretti, S.,, S. Bellocchio,, P. Bonifazi,, S. Bozza,, T. Zelante,, F. Bistoni, and, L. Romani. 2008. The contribution of PARs to inflammation and immunity to fungi. Mucosal Immunol. 1:156168.
50. Netea, M. G.,, G. D. Brown,, B. J. Kullberg, and, N. A. Gow. 2008. An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol. 6:6778.
51. Netea, M. G.,, N. A. Gow,, C. A. Munro,, S. Bates,, C. Collins,, G. Ferwerda,, R. P. Hobson,, G. Bertram,, H. B. Hughes,, T. Jansen,, L. Jacobs,, E. T. Buurman,, K. Gijzen,, D. L. Williams,, R. Torensma,, A. McKinnon,, D. M. MacCallum,, F. C. Odds,, J. W. Van der Meer,, A. J. Brown, and, B. J. Kullberg. 2006. Immune sensing of Candida albicans requires cooperative recognition of mannans and glu-cans by lectin and Toll-like receptors. J. Clin. Investig. 116:16421650.
52. Netea, M. G.,, B. J. Kullberg, and, J. W. van der Meer. 2005. Severely impaired IL-12/IL-18/IFNγ axis in patients with hyper IgE syndrome. Eur. J. Clin. Investig. 35:718721.
53. Netea, M. G.,, R. Sutmuller,, C. Hermann,, C. A. Van der Graaf,, J. W. Van der Meer,, J. H. van Krieken,, T. Hartung,, G. Adema, and, B. J. Kullberg. 2004. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J. Immunol. 172:37123718.
54. Odds, F. C.,, and M. D. Jacobsen. 2008. Multilocus sequence typing of pathogenic Candida species. Eukaryot. Cell 7:10751084.
55. Orabona, C.,, U. Grohmann,, M. L. Belladonna,, F. Fallarino,, C. Vacca,, R. Bianchi,, S. Bozza,, C. Volpi,, B. L. Salomon,, M. C. Fioretti,, L. Romani, and, P. Puccetti. 2004. CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat. Immunol. 5:11341142.
56. Pfaller, M. A.,, and D. J. Diekema. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20:133163.
57. Pirofski, L. A.,, and A. Casadevall. 2006. Acquired antibody-mediated immunity to fungi, p. 487–503. In J. Heitman,, S. G. Filler,, J. E. Edwards, and, A. P. Mitchell (ed.), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC.
58. Reid, D. M.,, N. A. Gow, and, G. D. Brown. 2009. Pattern recognition: recent insights from Dectin-1. Curr. Opin. Immunol. 21:3037.
59. Rizzetto, L.,, M. Kuka,, C. De Filippo,, A. Cambi,, M. G. Netea,, L. Beltrame,, G. Napolitani,, M. G. Torcia,, U. D’Oro, and, D. Cavalieri. 2010. Differential IL-17 production and mannan recognition contribute to fungal pathogenicity and commensalism. J. Immunol. 184:42584268.
60. Robinson, M. J.,, F. Osorio,, M. Rosas,, R. P. Freitas,, E. Schweighoffer,, O. Gross,, J. S. Verbeek,, J. Ruland,, V. Tybulewicz,, G. D. Brown,, L. F. Moita,, P. R. Taylor, and, C. Reis e Sousa. 2009. Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J. Exp. Med. 206:20372051.
61. Romagnani, S.,, E. Maggi,, F. Liotta,, L. Cosmi, and, F. Annunziato. 2009. Properties and origin of human Th17 cells. Mol. Immunol. 47:37.
62. Romani, L. 2011. Immunity to fungal infections. Nat. Rev. Immunol. 11:275288.
63. Romani, L. 2004. Immunity to fungal infections. Nat. Rev. Immunol. 4:123.
64. Romani, L.,, F. Bistoni, and, P. Puccetti. 2002. Fungi, dendritic cells and receptors: a host perspective of fungal virulence. Trends Microbiol. 10:508514.
65. Romani, L.,, C. Montagnoli,, S. Bozza,, K. Perruccio,, A. Spreca,, P. Allavena,, S. Verbeek,, R. A. Calderone,, F. Bistoni, and, P. Puccetti. 2004. The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicans. Int. Immunol. 16:149161.
66. Romani, L.,, and P. Puccetti. 2006. Protective tolerance to fungi: the role of IL-10 and tryptophan catabolism. Trends Microbiol. 14:183189.
67. Romani, L.,, T. Zelante,, A. De Luca,, F. Fallarino, and, P. Puccetti. 2008. IL-17 and therapeutic kynurenines in pathogenic inflammation to fungi. J. Immunol. 180:51575162.
68. Ruas, L. P.,, E. S. Bernardes,, M. L. Fermino,, L. L. de Oliveira,, D. K. Hsu,, F. T. Liu,, R. Chammas, and, M. C. Roque-Barreira. 2009. Lack of galectin-3 drives response to Paracoccidioides brasiliensis toward a Th2-biased immunity. PLoS One 4:e4519.
69. Ryan, K. R.,, M. Hong,, P. D. Arkwright,, A. R. Gennery,, C. Costigan,, M. Dominguez,, D. Denning,, V. McConnell,, A. J. Cant,, M. Abinun,, G. P. Spickett, and, D. Lilic. 2008. Impaired dendritic cell maturation and cytokine production in patients with chronic mucocutanous [sic] candidiasis with or without APECED. Clin. Exp. Immunol. 154:406414.
70. Ryan, K. R.,, C. A. Lawson,, A. R. Lorenzi,, P. D. Arkwright,, J. D. Isaacs, and, D. Lilic. 2005. CD4 +CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J. Allergy Clin. Immunol. 116:11581159.
71. Saijo, S.,, S. Ikeda,, K. Yamabe,, S. Kakuta,, H. Ishigame,, A. Akitsu,, N. Fujikado,, T. Kusaka,, S. Kubo,, S. H. Chung,, R. Komatsu,, N. Miura,, Y. Adachi,, N. Ohno,, K. Shibuya,, N. Yamamoto,, K. Kawakami,, S. Yamasaki,, T. Saito,, S. Akira, and, Y. Iwakura. 2010. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32:681691.
72. Sato, K.,, X. L. Yang,, T. Yudate,, J. S. Chung,, J. Wu,, K. Luby-Phelps,, R. P. Kimberly,, D. Underhill,, P. D. Cruz, Jr., and, K. Ariizumi. 2006. Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. J. Biol. Chem. 281:3885438866.
73. Schneider, D. S.,, and J. S. Ayres. 2008. Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat. Rev. Immunol. 8:889895.
74. Sganga, G. 2009. Clinical aspects of invasive candidiasis in the surgical patient. Drugs 69(Suppl. 1):2932.
75. Singh, N.,, and J. R. Perfect. 2007. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect. Dis. 7:395401.
76. Sundrud, M. S.,, S. B. Koralov,, M. Feuerer,, D. P. Calado,, A. E. Kozhaya,, A. Rhule-Smith,, R. E. Lefebvre,, D. Unutmaz,, R. Mazitschek,, H. Waldner,, M. Whitman,, T. Keller, and, A. Rao. 2009. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 324:13341338.
77. Talloczy, Z.,, J. Martinez,, D. Joset,, Y. Ray,, A. Gacser,, S. Toussi,, N. Mizushima,, J. D. Nosanchuk,, H. Goldstein,, J. Loike,, D. Sulzer, and, L. Santambrogio. 2008. Methamphetamine inhibits antigen processing, presentation, and phagocytosis. PLoS Pathog. 4:e28.
78. Taylor, P. R.,, S. V. Tsoni,, J. A. Willment,, K. M. Dennehy,, M. Rosas,, H. Findon,, K. Haynes,, C. Steele,, M. Botto,, S. Gordon, and, G. D. Brown. 2007. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat. Immunol. 8:3138.
79. van de Veerdonk, F. L.,, R. J. Marijnissen,, B. J. Kullberg,, H. J. Koenen,, S. C. Cheng,, I. Joosten,, W. B. van den Berg,, D. L. Williams,, J. W. van der Meer,, L. A. Joosten, and, M. G. Netea. 2009. The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe 5:329340.
80. van de Veerdonk, F. L.,, M. G. Netea,, L. A. Joosten,, J. W. van der Meer, and, B. J. Kullberg. 2010. Novel strategies for the prevention and treatment of Candida infections: the potential of immunotherapy. FEMS Microbiol Rev. 34:10631075.
81. van Spriel, A. B.,, M. Sofi,, K. H. Gartlan,, A. van der Schaaf,, I. Verschueren,, R. Torensma,, R. A. Raymakers,, B. E. Loveland,, M. G. Netea,, G. J. Adema,, M. D. Wright, and, C. G. Figdor. 2009. The tetraspanin protein CD37 regulates IgA responses and antifungal immunity. PLoS Pathog. 5:e1000338.
82. Venditti, M. 2009. Clinical aspects of invasive candidiasis: endocarditis and other localized infections. Drugs 69(Suppl. 1):3943.
83. Villamon, E.,, D. Gozalbo,, P. Roig,, J. E. O’Connor,, D. Fradelizi, and, M. L. Gil. 2004. Toll-like receptor-2 is essential in murine defenses against Candida albicans infections. Microbes Infect. 6:17.
84. Wells, C. A.,, J. A. Salvage-Jones,, X. Li,, K. Hitchens,, S. Butcher,, R. Z. Murray,, A. G. Beckhouse,, Y. L. Lo,, S. Manzanero,, C. Cobbold,, K. Schroder,, B. Ma,, S. Orr,, L. Stewart,, D. Lebus,, P. Sobieszczuk,, D. A. Hume,, J. Stow,, H. Blanchard, and, R. B. Ashman. 2008. The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans. J. Immunol. 180:74047413.
85. Yamasaki, S.,, E. Ishikawa,, M. Sakuma,, H. Hara,, K. Ogata, and, T. Saito. 2008. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat. Immunol. 9:11791188.
86. Yamasaki, S.,, M. Matsumoto,, O. Takeuchi,, T. Matsuzawa,, E. Ishikawa,, M. Sakuma,, H. Tateno,, J. Uno,, J. Hirabayashi,, Y. Mikami,, K. Takeda,, S. Akira, and, T. Saito. 2009. C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. Proc. Natl. Acad. Sci. USA 106:18971902.
87. Zelante, T.,, A. De Luca,, P. Bonifazi,, C. Montagnoli,, S. Bozza,, S. Moretti,, M. L. Belladonna,, C. Vacca,, C. Conte,, P. Mosci,, F. Bistoni,, P. Puccetti,, R. A. Kastelein,, M. Kopf, and, L. Romani. 2007. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur. J. Immunol. 37:26952706.
88. Zelante, T.,, A. De Luca,, C. D’Angelo,, S. Moretti, and, L. Romani. 2009. IL-17/Th17 in antifungal immunity: what’s new? Eur. J. Immunol. 39:645648.
89. Zelante, T.,, F. Fallarino,, F. Bistoni,, P. Puccetti, and, L. Romani. 2009. Indoleamine 2,3-dioxygenase in infection: the paradox of an evasive strategy that benefits the host. Microbes Infect. 11:133141.
90. Zenewicz, L. A.,, and R. A. Flavell. 2008. IL-22 and inflammation: leukin’ through a glass onion. Eur. J. Immunol. 38:32653268.
91. Zhou, L.,, M. M. Chong, and, D. R. Littman. 2009. Plasticity of CD4+ T cell lineage differentiation. Immunity 30:646655.

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