Chapter 33 : Pulmonary Innate and Adaptive Defenses against

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Pulmonary Innate and Adaptive Defenses against , Page 1 of 2

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Clinical and experimental studies clearly substantiate the role of acquired cell-mediated immunity in the establishment of long-term protection against pulmonary cryptococcosis. However, the innate immune system is also centrally involved in both immediate antifungal immune responses as well as promoting adaptive immunity. Surfactant is secreted by type II cells in the alveolar space of the lung, and it is composed of a complex mixture of phospholipids and proteins, including surfactant proteins A and D (SP-A, SP-D), which play a role in innate host defense. Complement plays an important role during innate immune responses to cells in extrapulmonary sites as a consequence of its ability to bind to encapsulated yeast cells and function as an opsonin. Toll-like receptors (TLRs) have been implicated in airway inflammation, and recent evidence suggests the involvement of certain TLRs in mediating a protective response by promoting a Th1-type T-cell adaptive immune response. enters the pulmonary system in both a spore and yeast form and has the ability to remain dormant for many years within the phagosomal compartment before infection is activated. The immune response to this organism is flexible and involves both cellular and humoral factors. However, environmental, genetic, or cryptococcal factors can exert pressures on this flexible program of host defense, leading to chronic and/or progressive infections, including disseminated disease.

Citation: Williams K, Wormley, Jr. F, Geunes-Boyer S, Wright J, Huffnagle G. 2011. Pulmonary Innate and Adaptive Defenses against , p 451-464. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch33

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1. Aguirre, K.,, E. A. Havell,, G. W. Gibson, and, L. L. Johnson. 1995. Role of tumor necrosis factor and gamma interferon in acquired resistance to Cryptococcus neoformans in the central nervous system of mice. Infect. Immun. 63:17251731.
2. Allen, M.,, D. Voelker, and, R. Mason. 2001. Interactions of surfactant proteins A and D with Saccharomyces cerevisiae and Aspergillus fumigatus. Infect. Immun. 69:20372044.
3. Alvarez, M., and, A. Casadevall. 2006. Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr. Biol. 16:21612165.
4. Alvarez, M.,, C. Saylor, and, A. Casadevall. 2008. Antibody action after phagocytosis promotes Cryptococcus neoformans and Cryptococcus gattii macrophage exocytosis with biofilm-like microcolony formation. Cell. Microbiol. 10:16221633.
5. Arora,, S.,, Y. Hernandez,, J. Erb-Downward,, R. McDonald,, G. Toews, and, G. Huffnagle. 2005. Role of IFN-gamma in regulating T2 immunity and the development of alternatively activated macrophages during allergic bronchopulmonary mycosis. J. Immunol. 174:63466356.
6. Atochina,, E.,, A. Gow,, J. Beck,, A. Haczku,, A. Inch,, H. Kadire,, Y. Tomer,, C. Davis,, A. Preston,, F. Poulain,, S. Hawgood, and, M. Beers. 2004. Delayed clearance of Pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J. Infect. Dis. 189:15281539.
7. Bauman, S. K.,, G. B. Huffnagle, and, J. W. Murphy. 2003. Effects of tumor necrosis factor alpha on dendritic cell accumulation in lymph nodes draining the immunization site and the impact on the anticryptococcal cell-mediated immune response. Infect. Immun. 71:6874.
8. Biondo,, C.,, A. Midiri,, M. Gambuzza,, E. Gerace,, M. Falduto,, R. Galbo,, A. Bellantoni,, C. Beninati,, G. Teti,, T. Leanderson, and, G. Mancuso. 2008. IFN-alpha/beta signaling is required for polarization of cytokine responses toward a protective type 1 pattern during experimental cryptococcosis. J. Immunol. 181:566573.
9. Biondo,, C.,, A. Midiri,, L. Messina,, F. Tomasello,, G. Garufi, M. R. Catania,, M. Bombaci,, C. Beninati,, G. Teti, and, G. Mancuso. 2005. MyD88 and TLR2, but not TLR4, are required for host defense against Cryptococcus neoformans. Eur. J. Immunol. 35:870878.
10. Bronte,, V.,, E. Apolloni,, A. Cabrelle,, R. Ronca,, P. Sera-fini,, P. Zamboni,, N. P. Restifo, and, P. Zanovello. 2000. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96:38383846.
11. Brummer, E., and, D. Stevens. 1994. Anticryptococcal activity of macrophages: role of mouse strain, C5, contact, phagocytosis, and Larginine. Cell Immunol. 157:110.
12. Bulmer, G. S., and, M. D. Sans. 1967. Cryptococcus neoformans. II. Phagocytosis by human leukocytes. J. Bacteriol. 94:14801483.
13. Cambi, A., and, C. G. Figdor. 2003. Dual function of C-type lectin-like receptors in the immune system. Curr. Opin. Cell Biol. 15:539546.
14. Cameron,, M. L.,, D. L. Granger,, J. B. Weinberg,, W. J. Kozumbo, and, H. S. Koren. 1990. Human alveolar and peritoneal macrophages mediate fungistasis independently of L-arginine oxidation to nitrite or nitrate. Am. Rev. Respir. Dis. 142:13131319.
15. Casadevall,, A.,, W. Cleare,, M. Feldmesser,, A. Glatman-Freedman,, D. L. Goldman,, T. R. Kozel,, N. Lendvai,, J. Mukherjee,, L. A. Pirofski,, J. Rivera,, A. L. Rosas,, M. D. Scharff,, P. Valadon,, K. Westin, and, Z. Zhong. 1998. Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. Antimicrob. Agents Chemother. 42:14371446.
16. Casadevall, A., and, L. A. Pirofski. 2003. The damageresponse framework of microbial pathogenesis. Nat. Rev. Microbiol. 1:1724.
17. Cauley, L. K., and, J. W. Murphy. 1979. Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect. Immun. 23:644651.
18. Charlier,, C.,, K. Nielsen,, S. Daou,, M. Brigitte,, F. Chretien, and, F. Dromer. 2008. Evidence for a role of monocytes in dissemination and brain invasion by Cryptococcus neoformans. Infect. Immun. 77:120127.
19. Chen,, G. H.,, J. L. Curtis,, C. H. Mody,, P. J. Christensen,, L. R. Armstrong, and, G. B. Toews. 1994. Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro. J. Immunol. 152:724734.
20. Chen,, G. H.,, R. A. McDonald,, J. C. Wells,, G. B. Huffnagle,, N. W. Lukacs, and, G. B. Toews. 2005. The gamma interferon receptor is required for the protective pulmonary inflammatory response to Cryptococcus neoformans. Infect. Immun. 73:17881796.
21. Chen,, G. H.,, D. A. McNamara,, Y. Hernandez, G. B. Huffnagle,, G. B. Toews, and, M. A. Olszewski. 2008. Inheritance of immune polarization patterns is linked to resistance versus susceptibility to Cryptococcus neoformans in a mouse model. Infect. Immun. 76:23792391.
22. Chen,, Y. C.,, S. C. Chang,, C. C. Shih,, C. C. Hung,, K. T. Luhd,, Y. S. Pan, and, W. C. Hsieh. 2000. Clinical features and in vitro susceptibilities of two varieties of Cryptococcus neoformans in Taiwan. Diagn. Microbiol. Infect. Dis. 36:175183.
23. Chuck, S. L., and, M. A. Sande. 1989. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N. Engl. J. Med. 321:794799.
24. Cleare, W., and, A. Casadevall. 1998. The different binding patterns of two immunoglobulin M monoclonal antibodies to Cryptococcus neoformans serotype A and D strains correlate with serotype classification and differences in functional assays. Clin. Diagn. Lab. Immunol. 5:125129.
25. Clemons, K. V.,, E. Brummer, and, D. A. Stevens. 1994. Cytokine treatment of central nervous system infection: efficacy of interleukin-12 alone and synergy with conventional antifungal therapy in experimental cryptococcosis. Antimicrob. Agents Chemother. 38:460464.
26. Collins, H. L., and, G. J. Bancroft. 1992. Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans. Eur. J. Immunol. 22:14471454.
27. Collins, V. P.,, A. Gellhorn, and, J. R. Trimble. 1995. The coincidence of cryptococcosis and disease of the reticulo-endothelial and lymphatic systems. Cancer 4:883889.
28. Dan,, J. M.,, R. M. Kelly,, C. K. Lee, and, S. M. Levitz. 2008. Role of the mannose receptor in a murine model of Cryptococcus neoformans infection. Infect. Immun. 76:23622367.
29. Decken,, K.,, G. Kohler,, K. Palmer-Lehmann,, A. Wunderlin,, F. Mattner,, J. Magram,, M. K. Gately, and, G. Alber. 1998. Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans. Infect. Immun. 66:49945000.
30. De Groot, P. W.,, A. F. Ram, and, F. M. Klis. 2005. Features and functions of covalently linked proteins in fungal cell walls. Fungal Genet. Biol. 42:657675.
31. Diamond, R. D., and, J. E. Bennett. 1974. Prognostic factors in cryptococcal meningitis. Ann. Intern. Med. 80:176181.
32. Diamond, R. D.,, R. K. Root, and, J. E. Bennett. 1972. Factors influencing killing of Cryptococcus neoformans by human leukocytes in vitro. J. Infect. Dis. 125:367376.
33. Dismukes, W. E. 1988. Cryptococcal meningitis in patients with AIDS. J. Infect. Dis. 157:624628.
34. Dong, Z. M., and, J. W. Murphy. 1997. Cryptococcal polysaccharides bind to CD18 on human neutrophils. Infect. Immun. 65:557563.
35. Duperval, R.,, P. E. Hermans,, N. S. Brewer, and, G. S. Roberts. 1977. Cryptococcosis, with emphasis on the significance of isolation of Cryptococcus neoformans from the respiratory tract. Chest 72:1319.
36. Eng, R. H.,, E. Bishburg,, S. M. Smith, and, R. Kapila. 1986. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am. J. Med. 81:1923.
37. Feldmesser, M., and, A. Casadevall. 1997. Effect of serum IgG1 to Cryptococcus neoformans glucuronoxylomannan on murine pulmonary infection. J. Immunol. 158:790799.
38. Feldmesser, M., and, A. Casadevall. 1998. Mechanism of action of antibody to capsular polysaccharide in Cryptococcus neoformans infection. Front Biosci. 3:d136–d151.
39. Feldmesser, M.,, A. Mednick, and, A. Casadevall. 2002. Antibody-mediated protection in murine Cryptococcus neoformans infection is associated with pleotrophic effects on cytokine and leukocyte responses. Infect. Immun. 70:15711580.
40. Feldmesser, M.,, S. Tucker, and, A. Casadevall. 2001. Intracellular parasitism of macrophages by Cryptococcus neoformans. Trends Microbiol. 9:273278.
41. Fingeroth, J.,, M. Benedict,, D. Levy, and, J. Strominger. 1989. Identification of murine complement receptor type 2. Proc. Natl. Acad. Sci. USA 86:242246.
42. Fingeroth, J.,, M. Heath, and, D. Ambrosino. 1989. Proliferation of resting B cells is modulated by CR2 and CR1. Immunol. Lett. 21:291301.
43. Fisher, D.,, J. Burrow,, D. Lo, and, B. Currie. 1993. Cryptococcus neoformans in tropical northern Australia: predominantly variant gattii with good outcomes. Aust. N. Z. J. Med. 23:678682.
44. Flesch, I. E.,, G. Schwamberger, and, S. H. Kaufmann. 1989. Fungicidal activity of IFN-gamma-activated macrophages extracellular killing of Cryptococcus neoformans. J. Immunol. 142:32193224.
45. Frade,, J. M.,, M. Mellado, G. del Real,, J. C. Gutierrez-Ramos,, P. Lind, and, A. C. Martinez. 1997. Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells. J. Immunol. 159:55765584.
46. Gal,, A. A.,, M. N. Koss,, J. Hawkins,, S. Evans, and, H. Einstein. 1986. The pathology of pulmonary cryptococcal infections in the acquired immunodeficiency syndrome. Arch. Pathol. Lab. Med. 110:502507.
47. Garcia-Hermoso, D.,, F. Dromer, and, G. Janbon. 2004. Cryptococcus neoformans capsule structure evolution in vitro and during murine infection. Infect. Immun. 72:33593365.
48. Garcia-Hermoso, D.,, F. Dromer,, S. Mathoulin-Pelissier, and, G. Janbon. 2001. Are two Cryptococcus neoformans strains epidemiologically linked? J. Clin. Microbiol. 39:14021406.
49. Garcia-Hermoso, D.,, G. Janbon, and, F. Dromer. 1999. Epidemiological evidence for dormant Cryptococcus neoformans infection. J. Clin. Microbiol. 37:32043209.
50. Geissmann, F.,, S. Jung, and, D. R. Littman. 2003. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:7182.
51. Gendel, B. R.,, M. Ende, and, S. L. Norman. 1950. Cryptococcosis: a review with special reference to apparent association with Hodgkin’s disease. Am. J. Med. 9:343355.
52. Giles, S.,, A. Zaas,, M. Reidy,, J. Perfect, and, J. Wright. 2007. Cryptococcus neoformans is resistant to surfactant protein A mediated host defense mechanisms. PLoS ONE 2:e1370.
53. Goerdt,, S.,, O. Politz,, K. Schledzewski,, R. Birk,, A. Gratchev,, P. Guillot,, N. Hakiy,, C. D. Klemke,, E. Dippel,, V. Kodelja, and, C. E. Orfanos. 1999. Alternative versus classical activation of macrophages. Pathobiology 67:222226.
54. Goldman, D.,, Y. Cho,, M. Zhao,, A. Casadevall, and, S. C. Lee. 1996. Expression of inducible nitric oxide synthase in rat pulmonary Cryptococcus neoformans granulomas. Am. J. Pathol. 148:12751282.
55. Goldman, D.,, S. C. Lee, and, A. Casadevall. 1994. Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat. Infect. Immun. 62:47554761.
56. Goldman,, D. L.,, S. C. Lee,, A. J. Mednick,, L. Montella, and, A. Casadevall. 2000. Persistent Cryptococcus neoformans pulmonary infection in the rat is associated with intracellular parasitism, decreased inducible nitric oxide synthase expression, and altered antibody responsiveness to cryptococcal polysaccharide. Infect. Immun. 68:832838.
57. Goldstein, E., and, O. N. Rambo. 1962. Cryptococcal infection following steroid therapy. Ann. Intern. Med. 56:114120.
58. Gordon, S. 2003. Alternative activation of macrophages. Nat. Rev. Immunol. 3:2335.
59. Graybill, J. R.,, R. Bocanegra,, C. Lambros, and, M. F. Luther. 1997. Granulocyte colony stimulating factor therapy of experimental cryptococcal meningitis. J. Med. Vet. Mycol. 35:243247.
60. Graybill, J. R., and, D. J. Drutz. 1978. Host defense in cryptococcosis. II. Cryptococcosis in the nude mouse. Cell. Immunol. 40:263274.
61. Gross,, O.,, A. Gewies,, K. Finger,, M. Schafer,, T. Sparwasser,, C. Peschel,, I. Forster, and, J. Ruland. 2006. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442:651656.
62. Hernandez,, Y.,, S. Arora,, J. R. Erb-Downward,, R. A. McDonald,, G. B. Toews, and, G. B. Huffnagle. 2005. Distinct roles for IL-4 and IL-10 in regulating T2 immunity during allergic bronchopulmonary mycosis. J. Immunol. 174:10271036.
63. Herring,, A. C.,, N. R. Falkowski,, G. H. Chen,, R. A. McDonald,, G. B. Toews, and, G. B. Huffnagle. 2005. Transient neutralization of tumor necrosis factor alpha can produce a chronic fungal infection in an immunocompetent host: potential role of immature dendritic cells. Infect. Immun. 73:3949.
64. Herring,, A. C.,, J. Lee, R. A. McDonald,, G. B. Toews, and, G. B. Huffnagle. 2002. Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary Cryptococcus neoformans infection. Infect. Immun. 70:29592964.
65. Hesse,, M.,, M. Modolell,, A. C. La Flamme,, M. Schito, J. M. Fuentes,, A. W. Cheever,, E. J. Pearce, and, T. A. Wynn. 2001. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J. Immunol. 167:65336544.
66. Hill, J. O. 1992. CD4+ T cells cause multinucleated giant cells to form around Cryptococcus neoformans and confine the yeast within the primary site of infection in the respiratory tract. J. Exp. Med. 175:16851695.
67. Hoag,, K. A.,, M. F. Lipscomb,, A. A. Izzo, and, N. E. Street. 1997. IL-12 and IFN-gamma are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C B-17 mice. Am. J. Respir. Cell. Mol. Biol. 17:733739.
68. Hoag,, K. A.,, N. E. Street,, G. B. Huffnagle, and, M. F. Lipscomb. 1995. Early cytokine production in pulmonary Cryptococcus neoformans infections distinguishes susceptible and resistant mice. Am. J. Respir. Cell. Mol. Biol. 13:487495.
69. Huang,, C.,, S. H. Nong,, M. K. Mansour,, C. A. Specht, and, S. M. Levitz. 2002. Purification and characterization of a second immunoreactive mannoprotein from Cryptococcus neoformans that stimulates T-cell responses. Infect. Immun. 70:54855493.
70. Huffnagle,, G. B.,, M. B. Boyd,, N. E. Street, and, M. F. Lipscomb. 1998. IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6). J. Immunol. 160:23932400.
71. Huffnagle, G. B., and, M. F. Lipscomb. 1998. Cells and cytokines in pulmonary cryptococcosis. Res. Immunol. 149:387396.
72. Huffnagle,, G. B.,, M. F. Lipscomb,, J. A. Lovchik,, K. A. Hoag, and, N. E. Street. 1994. The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection. J. Leukoc. Biol. 55:3542.
73. Huffnagle,, G. B.,, L. K. McNeil,, R. A. McDonald,, J. W. Murphy,, G. B. Toews,, N. Maeda, and, W. A. Kuziel. 1999. Cutting edge: role of C-C chemokine receptor 5 in organspecific and innate immunity to Cryptococcus neoformans. J. Immunol. 163:46424646.
74. Huffnagle,, G. B.,, R. M. Strieter,, L. K. McNeil,, R. A. McDonald,, M. D. Burdick,, S. L. Kunkel, and, G. B. Toews. 1997. Macrophage inflammatory protein-1alpha (MIP-1alpha) is required for the efferent phase of pulmonary cell-mediated immunity to a Cryptococcus neoformans infection. J. Immunol. 159:318327.
75. Huffnagle,, G. B.,, R. M. Strieter,, T. J. Standiford,, R. A. McDonald,, M. D. Burdick,, S. L. Kunkel, and, G. B. Toews. 1995. The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection. J. Immunol. 155:47904797.
76. Huffnagle,, G. B.,, G. B. Toews,, M. D. Burdick,, M. B. Boyd,, K. S. McAllister,, R. A. McDonald,, S. L. Kunkel, and, R. M. Strieter. 1996. Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans. J. Immunol. 157:45294536.
77. Huffnagle, G. B.,, J. L. Yates, and, M. F. Lipscomb. 1991. Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells. J. Exp. Med. 173:793800.
78. Huffnagle, G. B.,, J. L. Yates, and, M. F. Lipscomb. 1991. T cell-mediated immunity in the lung: a Cryptococcus neoformans pulmonary infection model using SCID and athymic nude mice. Infect. Immun. 59:14231433.
79. Ibrahim,, A. S.,, S. G. Filler,, M. S. Alcouloumre,, T. R. Kozel,, J. E. Edwards, Jr., and, M. A. Ghannoum. 1995. Adherence to and damage of endothelial cells by Cryptococcus neoformans in vitro: role of the capsule. Infect. Immun. 63:43684374.
80. Joly, V.,, L. Saint-Julien,, C. Carbon, and, P. Yeni. 1994. In vivo activity of interferon-gamma in combination with amphotericin B in the treatment of experimental cryptococcosis. J. Infect. Dis. 170:13311334.
81. Kakeya,, H.,, H. Udono,, N. Ikuno,, Y. Yamamoto,, K. Mitsutake,, T. Miyazaki,, K. Tomono,, H. Koga,, T. Tashiro,, E. Nakayama, and, S. Kohno. 1997. A 77-kilodalton protein of Cryptococcus neoformans, a member of the heat shock protein 70 family, is a major antigen detected in the sera of mice with pulmonary cryptococcosis. Infect. Immun. 65:16531658.
82. Kakeya,, H.,, H. Udono,, S. Maesaki,, E. Sasaki,, S. Kawamura, M. A. Hossain,, Y. Yamamoto,, T. Sawai,, M. Fukuda,, K. Mitsutake,, Y. Miyazaki,, K. Tomono,, T. Tashiro,, E. Nakayama, and, S. Kohno. 1999. Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis. Clin. Exp. Immunol. 115:485490.
83. Kawakami,, K.,, Y. Kinjo,, K. Uezu,, S. Yara,, K. Miyagi,, Y. Koguchi,, T. Nakayama,, M. Taniguchi, and, A. Saito. 2001. Monocyte chemoattractant protein-1-dependent increase of V alpha 14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection. J. Immunol. 167:65256532.
84. Kawakami,, K.,, Y. Koguchi,, M. H. Qureshi,, Y. Kinjo,, S. Yara,, A. Miyazato,, M. Kurimoto,, K. Takeda,, S. Akira, and, A. Saito. 2000. Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice. FEMS Microbiol. Lett. 186:121126.
85. Kawakami,, K.,, Y. Koguchi,, M. H. Qureshi,, A. Miyazato,, S. Yara,, Y. Kinjo,, Y. Iwakura,, K. Takeda,, S. Akira,, M. Kurimoto, and, A. Saito. 2000. IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-gamma production by NK cells. J. Immunol. 165:941947.
86. Kawakami,, K.,, M. H. Qureshi,, T. Zhang,, Y. Koguchi,, K. Shibuya,, S. Naoe, and, A. Saito. 1999. Interferon-gamma (IFN-gamma)-dependent protection and synthesis of chemoattractants for mononuclear leucocytes caused by IL-12 in the lungs of mice infected with Cryptococcus neoformans. Clin. Exp. Immunol. 117:113122.
87. Kawakami,, K.,, M. H. Qureshi,, T. Zhang,, Y. Koguchi,, S. Yara,, K. Takeda,, S. Akira,, M. Kurimoto, and, A. Saito. 2000. Involvement of endogenously synthesized interleukin (IL)-18 in the protective effects of IL-12 against pulmonary infection with Cryptococcus neoformans in mice. FEMS Immunol. Med. Microbiol. 27:191200.
88. Kawakami,, K.,, M. H. Qureshi,, T. Zhang,, H. Okamura,, M. Kurimoto, and, A. Saito. 1997. IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-gamma production. J. Immunol. 159:55285534.
89. Kawakami, K.,, M. Tohyama,, X. Qifeng, and, A. Saito. 1997. Expression of cytokines and inducible nitric oxide synthase mRNA in the lungs of mice infected with Cryptococcus neoformans: effects of interleukin-12. Infect. Immun. 65:13071312.
90. Kawakami,, K.,, M. Tohyama,, K. Teruya,, N. Kudeken,, Q. Xie, and, A. Saito. 1996. Contribution of interferon-gamma in protecting mice during pulmonary and disseminated infection with Cryptococcus neoformans. FEMS Immunol. Med. Microbiol. 13:123130.
91. Kawakami, K.,, M. Tohyama,, Q. Xie, and, A. Saito. 1996. IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans. Clin. Exp. Immunol. 104:208214.
92. Kechichian, T. B.,, J. Shea, and, M. Del Poeta. 2007. Depletion of alveolar macrophages decreases the dissemination of a glucosylceramide-deficient mutant of Cryptococcus neoformans in immunodeficient mice. Infect. Immun. 75:47924798.
93. Keye, J. D., and, W. E. Magee. 1956. Fungal diseases in a general hospital. Am. J. Clin. Pathol. 2612351253.
94. Kleinschek,, M. A.,, U. Muller, S. J. Brodie,, W. Stenzel,, G. Kohler,, W. M. Blumenschein,, R. K. Straubinger,, T. McClanahan,, R. A. Kastelein, and, G. Alber. 2006. IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. J. Immunol. 176:10981106.
95. Kopp, E., and, R. Medzhitov. 2003. Recognition of microbial infection by Toll-like receptors. Curr. Opin. Immunol. 15:396401.
96. Kovacs,, J. A.,, A. A. Kovacs,, M. Polis, W. C. Wright,, V. J. Gill,, C. U. Tuazon,, E. P. Gelmann,, H. C. Lane,, R. Longfield, and, G. Overturf. 1985. Cryptococcosis in the acquired immunodeficiency syndrome. Ann. Intern. Med. 103:533538.
97. Kozel, T. R., and, J. Cazin, Jr. 1971. Nonencapsulated variant of Cryptococcus neoformans I. Virulence studies and characterization of soluble polysaccharide. Infect. Immun. 3:287294.
98. Kozel, T. R.,, B. Highison, and, C. J. Stratton. 1984. Localization on encapsulated Cryptococcus neoformans of serum components opsonic for phagocytosis by macrophages and neutrophils. Infect. Immun. 43:574579.
99. Levitz, S. M. 1991. Activation of human peripheral blood mononuclear cells by interleukin-2 and granulocyte-macrophage colony-stimulating factor to inhibit Cryptococcus neoformans. Infect. Immun. 59:33933397.
100. Levitz, S. M., and, D. J. DiBenedetto. 1988. Differential stimulation of murine resident peritoneal cells by selectively opsonized encapsulated and acapsular Cryptococcus neoformans. Infect. Immun. 56:25442551.
101. Levitz, S. M., and, M. P. Dupont. 1993. Phenotypic and functional characterization of human lymphocytes activated by interleukin-2 to directly inhibit growth of Cryptococcus neoformans in vitro. J. Clin. Invest. 91:14901498.
102. Levitz, S. M.,, M. P. Dupont, and, E. H. Smail. 1994. Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans. Infect. Immun. 62:194202.
103. Levitz,, S. M.,, S. Nong, M. K. Mansour,, C. Huang, and, C. A. Specht. 2001. Molecular characterization of a mannoprotein with homology to chitin deacetylases that stimulates T cell responses to Cryptococcus neoformans. Proc. Natl. Acad. Sci. USA 98:1042210427.
104. Levitz,, S. M.,, E. A. North,, M. P. Dupont, and, T. S. Harrison. 1995. Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes. Infect. Immun. 63:35503554.
105. Levitz, S. M., and, C. A. Specht. 2006. The molecular basis for the immunogenicity of Cryptococcus neoformans mannoproteins. FEMS Yeast Res. 6:513524.
106. Lewis, J. L., and, S. Rabinovich. 1972. The wide spectrum of cryptococcal infections. Am. J. Med. 53:315322.
107. Lindell,, D. M.,, T. A. Moore,, R. A. McDonald,, G. B. Toews, and, G. B. Huffnagle. 2006. Distinct compartmentalization of CD4+ T-cell effector function versus proliferative capacity during pulmonary cryptococcosis. Am. J. Pathol. 168:847855.
108. Lindell,, D. M.,, T. A. Moore,, R. A. McDonald,, G. B. Toews, and, G. B. Huffnagle. 2005. Generation of antifungal effector CD8+ T cells in the absence of CD4+ T cells during Cryptococcus neoformans infection. J. Immunol. 174:79207928.
109. Linke, M.,, A. Ashbaugh,, J. Koch,, R. Tanaka, and, P. Walzer. 2005. Surfactant protein A limits Pneumocystis murina infection in immunosuppressed C3H/HeN mice and modulates host response during infection. Microbes Infect. 7:748759.
110. Lovchik, J. A.,, C. R. Lyons, and, M. F. Lipscomb. 1995. A role for gamma interferon-induced nitric oxide in pulmonary clearance of Cryptococcus neoformans. Am. J. Respir. Cell. Mol. Biol. 13:116124.
111. Lovchik,, J. A.,, J. A. Wilder,, G. B. Huffnagle,, R. Riblet,, C. R. Lyons, and, M. F. Lipscomb. 1999. Ig heavy chain complex-linked genes influence the immune response in a murine cryptococcal infection. J. Immunol. 163:39073913.
112. Luberto,, C.,, B. Martinez-Marino,, D. Taraskiewicz,, B. Bolanos,, P. Chitano, D. L. Toffaletti,, G. M. Cox,, J. R. Perfect,, Y. A. Hannun,, E. Balish, and, M. Del Poeta. 2003. Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans. J. Clin. Invest. 112:10801094.
113. Ma, H.,, J. Croudace,, D. Lammas, and, R. May. 2007. Direct cell-to-cell spread of a pathogenic yeast. BMC Immunol. 8:15.
114. Ma,, L. L.,, J. C. Spurrell,, J. F. Wang,, G. G. Neely,, S. Epelman,, A. M. Krensky, and, C. H. Mody. 2002. CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15. J. Immunol. 169:57875795.
115. Madan,, T.,, U. Kishore,, M. Singh,, P. Strong,, H. Clark,, E. Hussain,, K. Reid, and, P. Sarma. 2001. Surfactant proteins A and D protect mice against pulmonary hyper-sensitivity induced by Aspergillus fumigatus antigens and allergens. J. Clin. Invest. 107:467475.
116. Madan,, T.,, U. Kishore,, M. Singh,, P. Strong,, E. Hussain,, K. Reid, and, P. Sarma. 2001. Protective role of lung surfactant protein D in a murine model of invasive pulmonary aspergillosis. Infect. Immun. 69:27282731.
117. Mansour, M. K.,, E. Latz, and, S. M. Levitz. 2006. Cryptococcus neoformans glycoantigens are captured by multiple lectin receptors and presented by dendritic cells. J. Immunol. 176:30533061.
118. Mansour, M. K.,, L. S. Schlesinger, and, S. M. Levitz. 2002. Optimal T cell responses to Cryptococcus neoformans mannoprotein are dependent on recognition of conjugated carbohydrates by mannose receptors. J. Immunol. 168:28722879.
119. Mansour,, M. K.,, L. E. Yauch,, J. B. Rottman, and, S. M. Levitz. 2004. Protective efficacy of antigenic fractions in mouse models of cryptococcosis. Infect. Immun. 72:17461754.
120. McGreal, E. P.,, J. L. Miller, and, S. Gordon. 2005. Ligand recognition by antigen-presenting cell C-type lectin receptors. Curr. Opin. Immunol. 17:1824.
121. Milam,, J. E.,, A. C. Herring-Palmer,, R. Pandrangi, R. A. McDonald,, G. B. Huffnagle, and, G. B. Toews. 2007. Modulation of the pulmonary type 2 T-cell response to Cryptococcus neoformans by intratracheal delivery of a tumor necrosis factor alpha-expressing adenoviral vector. Infect. Immun. 75:49514958.
122. Mody,, C. H.,, G. H. Chen,, C. Jackson, J. L. Curtis, and, G. B. Toews. 1993. Depletion of murine CD8+ T-cells in vivo decreases pulmonary clearance of a moderately virulent strain of Cryptococcus neoformans. J. Lab. Clin. Med. 121:765773.
123. Mody,, C. H.,, G. H. Chen,, C. Jackson, J. L. Curtis, and, G. B. Toews. 1994. In vivo depletion of murine CD8 positive T cells impairs survival during infection with a highly virulent strain of Cryptococcus neoformans. Myco-pathologia 125:717.
124. Mody,, C. H.,, M. F. Lipscomb,, N. E. Street, and, G. B. Toews. 1990. Depletion of CD4+ (L3T4+) lymphocytes in vivo impairs murine host defense to Cryptococcus neo-formans. J. Immunol. 144:14721477.
125. Mody,, C. H.,, C. L. Tyler,, R. G. Sitrin,, C. Jackson, and, G. B. Toews. 1991. Interferon-gamma activates rat alveolar macrophages for anticryptococcal activity. Am. J. Respir. Cell. Mol. Biol. 5:1926.
126. Mukherjee, J.,, T. R. Kozel, and, A. Casadevall. 1998. Monoclonal antibodies reveal additional epitopes of serotype D Cryptococcus neoformans capsular glucuronoxylomannan that elicit protective antibodies. J. Immunol. 161:35573568.
127. Mukherjee, S.,, M. Feldmesser, and, A. Casadevall. 1996. J774 murine macrophage-like cell interactions with Cryptococcus neoformans in the presence and absence of opsonins. J. Infect. Dis. 173:12221231.
128. Mukherjee, S.,, S. C. Lee, and, A. Casadevall. 1995. Antibodies to Cryptococcus neoformans glucuronoxylomannan enhance antifungal activity of murine macrophages. Infect. Immun. 63:573579.
129. Muller,, U.,, W. Stenzel,, G. Kohler,, C. Werner,, T. Polte,, G. Hansen,, N. Schutze,, R. K. Straubinger,, M. Blessing,, A. N. McKenzie,, F. Brombacher, and, G. Alber. 2007. IL-13 induces disease-promoting type 2 cytokines, alternatively activated macrophages and allergic inflammation during pulmonary infection of mice with Cryptococcus neoformans. J. Immunol. 179:53675377.
130. Murphy, J. W.,, M. R. Hidore, and, S. C. Wong. 1993. Direct interactions of human lymphocytes with the yeastlike organism, Cryptococcus neoformans. J. Clin. Invest. 91:15531566.
131. Murphy,, J. W.,, R. L. Mosley,, R. Cherniak, G. H. Reyes,, T. R. Kozel, and, E. Reiss. 1988. Serological, electrophoretic, and biological properties of Cryptococcus neoformans antigens. Infect. Immun. 56:424431.
132. Murphy, J. W.,, F. Schafer,, A. Casadevall, and, A. Adesina. 1998. Antigen-induced protective and nonprotective cell-mediated immune components against Cryptococcus neoformans. Infect. Immun. 66:26322639.
133. Muth, S. M., and, J. W. Murphy. 1995. Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans-immunized mice. Infect. Immun. 63:16371644.
134. Nakamura,, K.,, T. Kinjo,, S. Saijo,, A. Miyazato,, Y. Adachi,, N. Ohno,, J. Fujita,, M. Kaku,, Y. Iwakura, and, K. Kawakami. 2007. Dectin-1 is not required for the host defense to Cryptococcus neoformans. Microbiol. Immunol. 51:11151119.
135. Nakamura,, K.,, K. Miyagi,, Y. Koguchi,, Y. Kinjo,, K. Uezu,, T. Kinjo,, M. Akamine,, J. Fujita,, I. Kawamura,, M. Mitsuyama,, Y. Adachi,, N. Ohno,, K. Takeda,, S. Akira,, A. Miyazato,, M. Kaku, and, K. Kawakami. 2006. Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans. FEMS Immunol. Med. Microbiol. 47:148154.
136. Netea, M. G.,, J. W. Van der Meer, and, B. J. Kullberg. 2006. Role of the dual interaction of fungal pathogens with pattern recognition receptors in the activation and modulation of host defence. Clin. Microbiol. Infect. 12:404409.
137. Nussbaum, G.,, W. Cleare,, A. Casadevall, M. D. Scharff, and, P. Valadon. 1997. Epitope location in the Cryptococcus neoformans capsule is a determinant of antibody efficacy. J. Exp. Med. 185:685694.
138. Olszewski,, M. A.,, G. B. Huffnagle,, R. A. McDonald,, D. M. Lindell,, B. B. Moore,, D. N. Cook, and, G. B. Toews. 2000. The role of macrophage inflammatory protein-1 alpha/CCL3 in regulation of T cell-mediated immunity to Cryptococcus neoformans infection. J. Immunol. 165:64296436.
139. Olszewski,, M. A.,, G. B. Huffnagle,, T. R. Traynor,, R. A. McDonald,, D. N. Cook, and, G. B. Toews. 2001. Regulatory effects of macrophage inflammatory protein 1alpha/CCL3 on the development of immunity to Cryptococcus neoformans depend on expression of early inflammatory cytokines. Infect. Immun. 69:62566263.
140. Oppmann,, B.,, R. Lesley,, B. Blom, J. C. Timans,, Y. Xu,, B. Hunte,, F. Vega,, N. Yu,, J. Wang,, K. Singh,, F. Zonin,, E. Vaisberg,, T. Churakova,, M. Liu,, D. Gorman,, J. Wagner,, S. Zurawski,, Y. Liu,, J. S. Abrams,, K. W. Moore,, D. Rennick,, R. de Waal-Malefyt,, C. Hannum,, J. F. Bazan, and, R. A. Kastelein. 2000. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715725.
141. Osterholzer,, J. J.,, J. L. Curtis,, T. Polak,, T. Ames,, G. H. Chen,, R. McDonald,, G. B. Huffnagle, and, G. B. Toews. 2008. CCR2 mediates conventional dendritic cell recruitment and the formation of bronchovascular mononuclear cell infiltrates in the lungs of mice infected with Cryptococcus neoformans. J. Immunol. 181:610620.
142. Pena, S. V., and, A. M. Krensky. 1997. Granulysin, a new human cytolytic granule-associated protein with possible involvement in cell-mediated cytotoxicity. Semin. Immunol. 9:117125.
143. Pillemer, S.,, G. Tsokos,, S. Barbieri,, J. Balow, and, B. Golding. 1990. The CR2 receptor (CD21) shows increased expression in the more differentiated cells of an antigen-specific B cell line. Cell. Immunol. 125:386395.
144. Qureshi,, M. H.,, T. Zhang,, Y. Koguchi,, K. Nakashima,, H. Okamura,, M. Kurimoto, and, K. Kawakami. 1999. Combined effects of IL-12 and IL-18 on the clinical course and local cytokine production in murine pulmonary infection with Cryptococcus neoformans. Eur. J. Immunol. 29:643649.
145. Reeke,, G. N.,, Jr., J. W. Becker,, B. A. Cunningham,, G. R. Gunther,, J. L. Wang, and, G. M. Edelman. 1974. Relationships between the structure and activities of concanavalin A. Ann. NYAcad. Sci. 234:369382.
146. Rivera, J.,, J. Mukherjee,, L. M. Weiss, and, A. Casadevall. 2002. Antibody efficacy in murine pulmonary Cryptococcus neoformans infection: a role for nitric oxide. J. Immunol. 168:34193427.
147. Robben, P. M.,, M. LaRegina,, W. A. Kuziel, and, L. D. Sibley. 2005. Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis. J. Exp. Med. 201:17611769.
148. Rottman,, J. B.,, K. P. Ganley,, K. Williams,, L. Wu,, C. R. Mackay, and, D. J. Ringler. 1997. Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am. J. Pathol. 151:13411351.
149. Rudner,, X. L.,, K. I. Happel,, E. A. Young, and, J. E. Shellito. 2007. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect. Immun. 75:30553061.
150. Schelenz,, S.,, R. Malhotra,, R. B. Sim,, U. Holmskov, and, G. J. Bancroft. 1995. Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells. Infect. Immun. 63:33603366.
151. Shao,, X.,, A. Mednick,, M. Alvarez, N. van Rooijen,, A. Casadevall, and, D. L. Goldman. 2005. An innate immune system cell is a major determinant of species-related susceptibility differences to fungal pneumonia. J. Immunol. 175:32443251.
152. Stano,, P.,, V. Williams,, M. Villani,, E. Cymbalyuk,, A. Qureshi,, Y. Huang,, G. Morace,, C. Luberto,, S. Tomlinson, and, M. Del Poeta. 2009. App1: an antiphagocytic protein that binds to complement receptors 3 and 2. J. Immunol. 182:8491.
153. Stein, M.,, S. Keshav,, N. Harris, and, S. Gordon. 1992. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J. Exp. Med. 176:287292.
154. Takeda, K., and, S. Akira. 2004. TLR signaling pathways. Semin. Immunol. 16:39.
155. Traynor,, T. R.,, A. C. Herring,, M. E. Dorf,, W. A. Kuziel,, G. B. Toews, and, G. B. Huffnagle. 2002. Differential roles of CC chemokine ligand 2/monocyte chemotactic protein-1 and CCR2 in the development of T1 immunity. J. Immunol. 168:46594666.
156. Traynor,, T. R.,, W. A. Kuziel,, G. B. Toews, and, G. B. Huffnagle. 2000. CCR2 expression determines T1 versus T2 polarization during pulmonary Cryptococcus neoformans infection. J. Immunol. 164:20212027.
157. Tucker, S. C., and, A. Casadevall. 2002. Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm. Proc. Natl. Acad. Sci. USA 99:31653170.
158. Uezu,, K.,, K. Kawakami,, K. Miyagi,, Y. Kinjo,, T. Kinjo,, H. Ishikawa, and, A. Saito. 2004. Accumulation of gammadelta T cells in the lungs and their regulatory roles in Th1 response and host defense against pulmonary infection with Cryptococcus neoformans. J. Immunol. 172:76297634.
159. Vaccaro,, A. M.,, M. Tatti,, F. Ciaffoni,, R. Salvioli,, A. Barca, and, C. Scerch. 1997. Effect of saposins A and C on the enzymatic hydrolysis of liposomal glucosylceramide. J. Biol. Chem. 272:1686216867.
160. van de Wetering,, J. K.,, F. E. Coenjaerts,, A. B. Vaandrager,, L. M. van Golde, and, J. J. Batenburg. 2004. Aggregation of Cryptococcus neoformans by surfactant protein D is inhibited by its capsular component glucuronoxylomannan. Infect. Immun. 72:145153.
161. van Rozendaal, B.,, A. van Spriel,, J. van De Winkel, and, H. Haagsman. 2000. Role of pulmonary surfactant protein D in innate defense against Candida albicans. J. Infect. Dis. 182:917922.
162. Vecchiarelli,, A.,, D. Pietrella,, M. Dottorini,, C. Monari,, C. Retini,, T. Todisco, and, F. Bistoni. 1994. Encapsulation of Cryptococcus neoformans regulates fungicidal activity and the antigen presentation process in human alveolar macrophages. Clin. Exp. Immunol. 98:217223.
163. Vecchiarelli,, A.,, D. Pietrella,, P. Lupo,, F. Bistoni,, D. C. McFadden, and, A. Casadevall. 2003. The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation. J. Leukoc. Biol. 74:370378.
164. Vuk-Pavlovic,, Z.,, E. Mo,, C. Icenhour,, J. Standing,, J. Fisher, and, A. Limper. 2006. Surfactant protein D enhances Pneumocystis infection in immune-suppressed mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 290:L442–L449.
165. Wagner,, R. P.,, S. M. Levitz,, A. Tabuni, and, H. Kornfeld. 1992. HIV-1 envelope protein (gp120) inhibits the activity of human bronchoalveolar macrophages against Cryptococcus neoformans. Am. Rev. Respir. Dis. 146:14341438.
166. Walenkamp,, A. M.,, A. F. Verheul,, J. Scharringa, and, I. M. Hoepelman. 1999. Pulmonary surfactant protein A binds to Cryptococcus neoformans without promoting phagocytosis. Eur. J. Clin. Invest. 29:8392.
167. Weinberg, P. B.,, S. Becker,, D. L. Granger, and, H. S. Koren. 1987. Growth inhibition of Cryptococcus neoformans by human alveolar macrophages. Am. Rev. Respir. Dis. 136:12421247.
168. Wormley,, F. L.,, Jr., J. R. Perfect,, C. Steele, and, G. M. Cox. 2007. Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain. Infect. Immun. 75:14531462.
169. Wozniak, K. L., and, S. M. Levitz. 2008. Cryptococcus neoformans enters the endolysosomal pathway of dendritic cells and is killed by lysosomal components. Infect. Immun. 76:47644771.
170. Wuthrich, M.,, H. I. Filutowicz,, T. Warner,, G. S. Deepe, Jr., and, B. S. Klein. 2003. Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts. J. Exp. Med. 197:14051416.
171. Yamaguchi, H.,, Y. Komase,, M. Ikehara,, T. Yamamoto, and, T. Shinagawa. 2008. Disseminated cryptococcal infection with eosinophilia in a healthy person. J. Infect. Chemother. 14:319324.
172. Yauch,, L. E.,, M. K. Mansour,, S. Shoham, J. B. Rottman, and, S. M. Levitz. 2004. Involvement of CD14, tolllike receptors 2 and 4, and MyD88 in the host response to the fungal pathogen Cryptococcus neoformans in vivo. Infect. Immun. 72:53735382.
173. Zaragoza, O., and, A. Casadevall. 2004. Antibodies produced in response to Cryptococcus neoformans pulmonary infection in mice have characteristics of nonprotective antibodies. Infect. Immun. 72:42714274.
174. Zelante,, T.,, A. De De,, 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.
175. Zheng,, C. F.,, L. L. Ma,, G. J. Jones,, M. J. Gill,, A. M. Krensky,, P. Kubes, and, C. H. Mody. 2007. Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients. Blood 109:20492057.
176. Zhong, Z., and, L. A. Pirofski. 1998. Antifungal activity of a human antiglucuronoxylomannan antibody. Clin. Diagn. Lab. Immunol. 5:5864.

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