Innate host defenses against Cryptococcus neoformans

Journal of Microbiology

Volumn 54, Issue 3, 2016, Pages 202-211

  Hole, Camaron ^a   Wormley, Floyd L ^a  

^a UNIVERSITY OF TEXAS AT SAN ANTONIO   (United States)

Author keywords

Cryptococcus; Cryptococcus neoformans; fungal immunity; fungal pathogenesis; host fungal interactions

Indexed keywords

FUNGUS VACCINE;

ADAPTIVE IMMUNITY; ANIMAL; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOCOMPETENCE; IMMUNOCOMPROMISED PATIENT; IMMUNOLOGY; INNATE IMMUNITY; MICROBIOLOGY; MOLECULAR MODEL; PATHOGENICITY;

ADAPTIVE IMMUNITY; ANIMALS; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; FUNGAL VACCINES; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNITY, INNATE; IMMUNOCOMPETENCE; IMMUNOCOMPROMISED HOST; MODELS, MOLECULAR;

EID: 84959196715     PISSN: 12258873     EISSN: 19763794     Source Type: Journal    
DOI: 10.1007/s12275-016-5625-7     Document Type: Review

References (115)

1. Allen, J.E. and Sutherland, T.E. 2014. Host protective roles of type 2 immunity: parasite killing and tissue repair, flip sides of the same coin. Semin. Immunol.26, 329–340.
2. Alvarez, M. and Casadevall, A. 2006. Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr. Biol.16, 2161–2165.
3. Andama, A.O., den Boon, S., Meya, D., Cattamanchi, A., Worodria, W., Davis, J.L., Walter, N.D., Yoo, S.D., Kalema, N., Haller, B., et al. 2013. Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda. J. Acquir. Immune. Defic. Syndr.63, 189–194.
4. Aratani, Y., Kura, F., Watanabe, H., Akagawa, H., Takano, Y., Ishida-Okawara, A., Suzuki, K., Maeda, N., and Koyama, H. 2006. Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans. J. Med. Microbiol.55, 1291–1299.
5. Arora, S., Hernandez, Y., Erb-Downward, J.R., McDonald, R.A., Toews, G.B., and Huffnagle, G.B. 2005. Role of IFN-gamma in regulating T2 immunity and the development of alternatively activated macrophages during allergic bronchopulmonary mycosis. J. Immunol.174, 6346–6356.
6. Arora, S., Olszewski, M.A., Tsang, T.M., McDonald, R.A., Toews, G.B., and Huffnagle, G.B. 2011. Effect of cytokine interplay on macrophage polarization during chronic pulmonary infection with Cryptococcus neoformans. Infect. Immun.79, 1915–1926.
7. Baddley, J.W., Perfect, J.R., Oster, R.A., Larsen, R.A., Pankey, G.A., Henderson, H., Haas, D.W., Kauffman, C.A., Patel, R., Zaas, A.K., et al. 2008. Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease. Eur. J. Clin. Microbiol. Infect. Dis.27, 937–943.
8. Bauman, S.K., Nichols, K.L., and Murphy, J.W. 2000. Dendritic cells in the induction of protective and nonprotective anticryptococcal cell-mediated immune responses. J. Immunol.165, 158–167.
9. Brena, S., Cabezas-Olcoz, J., Moragues, M.D., Fernandez de Larrinoa, I., Dominguez, A., Quindos, G., and Ponton, J. 2011. Fungicidal monoclonal antibody C7 interferes with iron acquisition in Candida albicans. Antimicrob. Agents Chemother.55, 3156–3163.
10. Casadevall, A. 1995. Antibody immunity and invasive fungal infections. Infect. Immun.63, 4211–4218.
11. Casadevall, A. and Pirofski, L.A. 2007. Antibody-mediated protection through cross-reactivity introduces a fungal heresy into immunological dogma. Infect. Immun.75, 5074–5078.
12. Charlier, C., Nielsen, K., Daou, S., Brigitte, M., Chretien, F., and Dromer, F. 2009. Evidence of a role for monocytes in dissemination and brain invasion by Cryptococcus neoformans. Infect. Immun.77, 120–127.
13. Chaturvedi, V., Flynn, T., Niehaus, W.G., and Wong, B. 1996. Stress tolerance and pathogenic potential of a mannitol mutant of Cryptococcus neoformans. Microbiology142 Pt 4, 937–943.
14. Chen, J., Varma, A., Diaz, M.R., Litvintseva, A.P., Wollenberg, K.K., and Kwon-Chung, K.J. 2008. Cryptococcus neoformans strains and infection in apparently immunocompetent patients, China. Emerg. Infect. Dis.14, 755–762.
15. Choi, K.H., Park, S.J., Min, K.H., Kim, S.R., Lee, M.H., Chung, C.R., Han, H.J., and Lee, Y.C. 2011. Treatment of asymptomatic pulmonary cryptococcosis in immunocompetent hosts with oral fluconazole. Scand. J. Infect. Dis.43, 380–385.
16. Coenjaerts, F.E., Walenkamp, A.M., Mwinzi, P.N., Scharringa, J., Dekker, H.A., van Strijp, J.A., Cherniak, R., and Hoepelman, A.I. 2001. Potent inhibition of neutrophil migration by cryptococcal mannoprotein-4-induced desensitization. J. Immunol.167, 3988–3995.
17. Dan, J.M., Kelly, R.M., Lee, C.K., and Levitz, S.M. 2008a. Role of the mannose receptor in a murine model of Cryptococcus neoformans infection. Infect. Immun.76, 2362–2367.
18. Dan, J.M., Wang, J.P., Lee, C.K., and Levitz, S.M. 2008b. Cooperative stimulation of dendritic cells by Cryptococcus neoformans mannoproteins and CpG oligodeoxynucleotides. PLoS One3, e2046.
19. Davis, M.J., Tsang, T.M., Qiu, Y., Dayrit, J.K., Freij, J.B., Huffnagle, G.B., and Olszewski, M.A. 2013. Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection. mBio4, e00264–13.
20. Ellerbroek, P.M., Lefeber, D.J., van Veghel, R., Scharringa, J., Brouwer, E., Gerwig, G.J., Janbon, G., Hoepelman, A.I., and Coenjaerts, F.E. 2004. O-acetylation of cryptococcal capsular glucuronoxylomannan is essential for interference with neutrophil migration. J. Immunol.173, 7513–7520.
21. Feldmesser, M., Casadevall, A., Kress, Y., Spira, G., and Orlofsky, A. 1997. Eosinophil-Cryptococcus neoformans interactions in vivo and in vitro. Infect. Immun.65, 1899–1907.
22. Garro, A.P., Chiapello, L.S., Baronetti, J.L., and Masih, D.T. 2011a. Eosinophils elicit proliferation of naive and fungal-specific cells in vivo so enhancing a T helper type 1 cytokine profile in favour of a protective immune response against Cryptococcus neoformans infection. Immunology134, 198–213.
23. Garro, A.P., Chiapello, L.S., Baronetti, J.L., and Masih, D.T. 2011b. Rat eosinophils stimulate the expansion of Cryptococcus neoformans- specific CD4+ and CD8+ T cells with a T-helper 1 profile. Immunology132, 174–187.
24. Gedik, H., Simsek, F., Kanturk, A., Yildirmak, T., Arica, D., Aydin, D., Demirel, N., and Yokus, O. 2014. Bloodstream infections in patients with hematological malignancies: which is more fatal - cancer or resistant pathogens? Ther. Clin. Risk Manag.10, 743–752.
25. Grahnert, A., Richter, T., Piehler, D., Eschke, M., Schulze, B., Muller, U., Protschka, M., Kohler, G., Sabat, R., Brombacher, F., et al. 2014. IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection. PLoS One9, e87341.
26. Grijpstra, J., Tefsen, B., van Die, I., and de Cock, H. 2009. The Cryptococcus neoformans cap10 and cap59 mutant strains, affected in glucuronoxylomannan synthesis, differentially activate human dendritic cells. FEMS Immunol. Med. Microbiol.57, 142–150.
27. Hardison, S.E., Herrera, G., Young, M.L., Hole, C.R., Wozniak, K.L., and Wormley, F.L.Jr. 2012. Protective immunity against pulmonary cryptococcosis is associated with STAT1-mediated classical macrophage activation. J. Immunol.189, 4060–4068.
28. Hardison, S.E., Ravi, S., Wozniak, K.L., Young, M.L., Olszewski, M.A., and Wormley, F.L.Jr. 2010a. Pulmonary infection with an interferon- gamma-producing Cryptococcus neoformans strain results in classical macrophage activation and protection. Am. J. Pathol.176, 774–785.
29. Hardison, S.E., Wozniak, K.L., Kolls, J.K., and Wormley, F.L.Jr. 2010b. Interleukin-17 is not required for classical macrophage activation in a pulmonary mouse model of Cryptococcus neoformans infection. Infect. Immun.78, 5341–5351.
30. Hole, C.R., Bui, H., Wormley, F.L.Jr., and Wozniak, K.L. 2012. Mechanisms of dendritic cell lysosomal killing of Cryptococcus. Sci. Rep.2, 739.
31. Holmer, S.M., Evans, K.S., Asfaw, Y.G., Saini, D., Schell, W.A., Ledford, J.G., Frothingham, R., Wright, J.R., Sempowski, G.D., and Perfect, J.R. 2014. Impact of surfactant protein D, interleukin- 5, and eosinophilia on Cryptococcosis. Infect. Immun.82, 683–693.
32. Huffnagle, G.B., Boyd, M.B., Street, N.E., and Lipscomb, M.F. 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, 2393–2400.
33. Huffnagle, G.B., Lipscomb, M.F., Lovchik, J.A., Hoag, K.A., and Street, N.E. 1994. The role of CD4+ and CD8+ T-cells in the protective inflammatory response to a pulmonary cryptococcal infection. J. Leukoc. Biol.55, 35–42.
34. Huffnagle, G.B., Yates, J.L., and Lipscomb, M.F. 1991. T-cell-mediated immunity in the lung - a Cryptococcus neoformans pulmonary infection model using SCID and athymic nude-mice. Infect. Immun.59, 1423–1433.
35. Humphreys, I.R., Edwards, L., Walzl, G., Rae, A.J., Dougan, G., Hill, S., and Hussell, T. 2003. OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia. J. Immunol.170, 6125–6132.
36. Husain, S., Wagener, M.M., and Singh, N. 2001. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg. Infect. Dis.7, 375–381.
37. Jain, A.V., Zhang, Y., Fields, W.B., McNamara, D.A., Choe, M.Y., Chen, G.H., Erb-Downward, J., Osterholzer, J.J., Toews, G.B., Huffnagle, G.B., et al. 2009. Th2 but not Th1 immune bias results in altered lung functions in a murine model of pulmonary Cryptococcus neoformans infection. Infect. Immun.77, 5389–5399.
38. Jarvis, J.N., Bicanic, T., Loyse, A., Namarika, D., Jackson, A., Nussbaum, J.C., Longley, N., Muzoora, C., Phulusa, J., Taseera, K., et al. 2014. Determinants of mortality in a combined cohort of 501 patients with HIV-associated Cryptococcal meningitis: implications for improving outcomes. Clin. Infect. Dis.58, 736–745.
39. Jones, G.J., Wiseman, J.C., Marr, K.J., Wei, S., Djeu, J.Y., and Mody, C.H. 2009. In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for Cryptococcus neoformans bypasses LFA-1. Int. Immunol.21, 423–432.
40. Kelly, R.M., Chen, J.M., Yauch, L.E., and Levitz, S.M. 2005. Opsonic requirements for dendritic cell-mediated responses to Cryptococcus neoformans. Infect. Immun.73, 592–598.
41. Kleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L.A., Ifrim, D.C., Saeed, S., Jacobs, C., van Loenhout, J., de Jong, D., Stunnenberg, H.G., et al. 2012. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc. Natl. Acad. Sci. USA109, 17537–17542.
42. Kleinschek, M.A., Muller, U., Schutze, N., Sabat, R., Straubinger, R.K., Blumenschein, W.M., McClanahan, T., Kastelein, R.A., and Alber, G. 2010. Administration of IL-23 engages innate and adaptive immune mechanisms during fungal infection. Int. Immunol.22, 81–90.
43. Kosmidis, C. and Denning, D.W. 2015. The clinical spectrum of pulmonary aspergillosis. Thorax70, 270–277.
44. Kramer, P.A., Ravi, S., Chacko, B., Johnson, M.S., and Darley-Usmar, V.M. 2014. A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers. Redox Biol.2, 206–210.
45. Leopold Wager, C.M., Hole, C.R., Wozniak, K.L., Olszewski, M.A., Mueller, M., and Wormley, F.L.Jr. 2015. STAT1 signaling within macrophages is required for anti-fungal activity against Cryptococcus neoformans. Infect. Immun.83, 4513–4527.
46. Leopold Wager, C.M., Hole, C.R., Wozniak, K.L., Olszewski, M.A., and Wormley, F.L.Jr. 2014. STAT1 Signaling is essential for protection against Cryptococcus neoformans infection in mice. J. Immunol.193, 4060–4071.
47. Leopold Wager, C.M. and Wormley, F.L. 2014. Classical versus alternative macrophage activation: the Ying and the Yang in host defense against pulmonary fungal infections. Mucosal Immunol.7, 1023–1035.
48. Levitz, S.M. 1991. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev. Infect. Dis.13, 1163–1169.
49. Li, S.S., Kyei, S.K., Timm-McCann, M., Ogbomo, H., Jones, G.J., Shi, M., Xiang, R.F., Oykhman, P., Huston, S.M., Islam, A., et al. 2013. The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients. Cell Host Microbe14, 387–397.
50. Loschi, M., Thill, C., Gray, C., David, M., Bagatha, M.F., Chamseddine, A., Contentin, N., Jardin, F., Lanic, H., Lemasle, E., et al. 2015. Invasive aspergillosis in neutropenic patients during hospital renovation: effectiveness of mechanical preventive measures in a prospective cohort of 438 patients. Mycopathologia179, 337–345.
51. Lupo, P., Chang, Y.C., Kelsall, B.L., Farber, J.M., Pietrella, D., Vecchiarelli, A., Leon, F., and Kwon-Chung, K.J. 2008. The presence of capsule in Cryptococcus neoformans influences the gene expression profile in dendritic cells during interaction with the fungus. Infect. Immun.76, 1581–1589.
52. Ma, L.L., Wang, C.L., Neely, G.G., Epelman, S., Krensky, A.M., and Mody, C.H. 2004. NK cells use perforin rather than granulysin for anticryptococcal activity. J. Immunol.173, 3357–3365.
53. Mambula, S.S., Simons, E.R., Hastey, R., Selsted, M.E., and Levitz, S.M. 2000. Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans. Infect. Immun.68, 6257–6264.
54. Mansour, M.K., Latz, E., and Levitz, S.M. 2006. Cryptococcus neoformans glycoantigens are captured by multiple lectin receptors and presented by dendritic cells. J. Immunol.176, 3053–3061.
55. Mansour, M.K., Schlesinger, L.S., and Levitz, S.M. 2002. Optimal T cell responses to Cryptococcus neoformans mannoprotein are dependent on recognition of conjugated carbohydrates by mannose receptors. J. Immunol.168, 2872–2879.
56. Marr, K.J., Jones, G.J., Zheng, C., Huston, S.M., Timm-McCann, M., Islam, A., Berenger, B.M., Ma, L.L., Wiseman, J.C., and Mody, C.H. 2009. Cryptococcus neoformans directly stimulates perforin production and rearms NK cells for enhanced anticryptococcal microbicidal activity. Infect. Immun.77, 2436–2446.
57. Martinez, L.R. and Casadevall, A. 2005. Specific antibody can prevent fungal biofilm formation and this effect correlates with protective efficacy. Infect. Immun.73, 6350–6362.
58. McClelland, E.E., Nicola, A.M., Prados-Rosales, R., and Casadevall, A. 2010. Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism. J. Clin. Invest.120, 1355–1361.
59. McNeill, E., Crabtree, M.J., Sahgal, N., Patel, J., Chuaiphichai, S., Iqbal, A.J., Hale, A.B., Greaves, D.R., and Channon, K.M. 2015. Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation. Free Radic. Biol. Med.79, 206–216.
60. Mednick, A.J., Feldmesser, M., Rivera, J., and Casadevall, A. 2003. Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis. Eur. J. Immunol.33, 1744–1753.
61. Milam, J.E., Herring-Palmer, A.C., Pandrangi, R., McDonald, R.A., Huffnagle, G.B., and Toews, G.B. 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, 4951–4958.
62. Mitchell, T.G. and Perfect, J.R. 1995. Cryptococcosis in the Era of AIDS - 100 years after the discovery of Cryptococcus neoformans. Clin. Microbiol. Rev.8, 515–548.
63. Muller, U., Stenzel, W., Kohler, G., Werner, C., Polte, T., Hansen, G., Schutze, N., Straubinger, R.K., Blessing, M., McKenzie, A.N., et al. 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, 5367–5377.
64. Murdock, B.J., Huffnagle, G.B., Olszewski, M.A., and Osterholzer, J.J. 2014. Interleukin-17A enhances host defense against cryptococcal lung infection through effects mediated by leukocyte recruitment, activation, and gamma interferon production. Infect. Immun.82, 937–948.
65. Murphy, J.W. 1998. Protective cell-mediated immunity against Cryptococcus neoformans. Res. Immunol.149, 373–386.
66. Nakamura, K., Miyazato, A., Xiao, G., Hatta, M., Inden, K., Aoyagi, T., Shiratori, K., Takeda, K., Akira, S., Saijo, S., et al. 2008. Deoxynucleic acids from Cryptococcus neoformans activate myeloid dendritic cells via a TLR9-dependent pathway. J. Immunol.180, 4067–4074.
67. Nakamura, Y., Sato, K., Yamamoto, H., Matsumura, K., Matsumoto, I., Nomura, T., Miyasaka, T., Ishii, K., Kanno, E., Tachi, M., et al. 2015. Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans. Infect. Immun.83, 671–681.
68. Netea, M.G., Quintin, J., and van der Meer, J.W. 2011. Trained immunity: a memory for innate host defense. Cell Host Microbe9, 355–361.
69. Nicola, A.M., Robertson, E.J., Albuquerque, P., Derengowski Lda, S., and Casadevall, A. 2011. Nonlytic exocytosis of Cryptococcus neoformans from macrophages occurs in vivo and is influenced by phagosomal pH. mBio2, e00167–11.
70. Olszewski, M.A., Huffnagle, G.B., Traynor, T.R., McDonald, R.A., Cook, D.N., and Toews, G.B. 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, 6256–6263.
71. Onishi, R.M. and Gaffen, S.L. 2010. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology129, 311–321.
72. Osterholzer, J.J., Chen, G.H., Olszewski, M.A., Curtis, J.L., Huffnagle, G.B., and Toews, G.B. 2009a. Accumulation of CD11b+ lung dendritic cells in response to fungal infection results from the CCR2-mediated recruitment and differentiation of Ly-6Chigh monocytes. J. Immunol.183, 8044–8053.
73. Osterholzer, J.J., Curtis, J.L., Polak, T., Ames, T., Chen, G.H., Mc- Donald, R., Huffnagle, G.B., and Toews, G.B. 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, 610–620.
74. Osterholzer, J.J., Milam, J.E., Chen, G.H., Toews, G.B., Huffnagle, G.B., and Olszewski, M.A. 2009b. Role of dendritic cells and alveolar macrophages in regulating early host defense against pulmonary infection with Cryptococcus neoformans. Infect. Immun.77, 3749–3758.
75. Osterholzer, J.J., Surana, R., Milam, J.E., Montano, G.T., Chen, G.H., Sonstein, J., Curtis, J.L., Huffnagle, G.B., Toews, G.B., and Olszewski, M.A. 2009c. Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung. Am. J. Pathol.174, 932–943.
76. Oykhman, P., Timm-McCann, M., Xiang, R.F., Islam, A., Li, S.S., Stack, D., Huston, S.M., Ma, L.L., and Mody, C.H. 2013. Requirement and redundancy of the Src family kinases Fyn and Lyn in perforin-dependent killing of Cryptococcus neoformans by NK cells. Infect. Immun.81, 3912–3922.
77. Oz, Y., Aslan, M., Aksit, F., Metintas, S., and Gunduz, E. 2015. The effect of clinical characteristics on the performance of galactomannan and PCR for the diagnosis of invasive aspergillosis in febrile neutropenic patients. Mycoses59, 86–92.
78. Panackal, A.A., Wuest, S.C., Lin, Y.C., Wu, T., Zhang, N., Kosa, P., Komori, M., Blake, A., Browne, S.K., Rosen, L.B., et al. 2015. Paradoxical immune responses in non-HIV Cryptococcal meningitis. PLoS Pathog.11, e1004884.
79. Pappas, P.G., Alexander, B.D., Andes, D.R., Hadley, S., Kauffman, C.A., Freifeld, A., Anaissie, E.J., Brumble, L.M., Herwaldt, L., Ito, J., et al. 2010. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin. Infect. Dis.50, 1101–1111.
80. Park, B.J., Wannemuehler, K.A., Marston, B.J., Govender, N., Pappas, P.G., and Chiller, T.M. 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS23, 525–530.
81. Piehler, D., Stenzel, W., Grahnert, A., Held, J., Richter, L., Kohler, G., Richter, T., Eschke, M., Alber, G., and Muller, U. 2011. Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis. Am. J. Pathol.179, 733–744.
82. Pietrella, D., Corbucci, C., Perito, S., Bistoni, G., and Vecchiarelli, A. 2005. Mannoproteins from Cryptococcus neoformans promote dendritic cell maturation and activation. Infect. Immun.73, 820–827.
83. Powderly, W.G. 1993. Cryptococcal meningitis and AIDS. Clin. Infect. Dis.17, 837–842.
84. Pyrgos, V., Seitz, A.E., Steiner, C.A., Prevots, D.R., and Williamson, P.R. 2013. Epidemiology of cryptococcal meningitis in the US: 1997-2009. PLoS One8, e56269.
85. Qiu, Y., Zeltzer, S., Zhang, Y., Wang, F., Chen, G.H., Dayrit, J., Murdock, B.J., Bhan, U., Toews, G.B., Osterholzer, J.J., et al. 2012. Early induction of CCL7 downstream of TLR9 signaling promotes the development of robust immunity to cryptococcal infection. J. Immunol.188, 3940–3948.
86. Quintin, J., Saeed, S., Martens, J.H., Giamarellos-Bourboulis, E.J., Ifrim, D.C., Logie, C., Jacobs, L., Jansen, T., Kullberg, B.J., Wijmenga, C., et al. 2012. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe12, 223–232.
87. Qureshi, A., Grey, A., Rose, K.L., Schey, K.L., and Del Poeta, M. 2011. Cryptococcus neoformans modulates extracellular killing by neutrophils. Front. Microbiol.2, 193.
88. Rocha, J.D., Nascimento, M.T., Decote-Ricardo, D., Corte-Real, S., Morrot, A., Heise, N., Nunes, M.P., Previato, J.O., Mendonca-Previato, L., DosReis, G.A., et al. 2015. Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils. Sci. Rep.5, 8008.
89. Rohatgi, S. and Pirofski, L.A. 2012. Molecular characterization of the early B cell response to pulmonary Cryptococcus neoformans infection. J. Immunol.189, 5820–5830.
90. Ruckerl, D. and Allen, J.E. 2014. Macrophage proliferation, provenance, and plasticity in macroparasite infection. Immunol. Rev.262, 113–133.
91. Saag, M.S., Graybill, R.J., Larsen, R.A., Pappas, P.G., Perfect, J.R., Powderly, W.G., Sobel, J.D., and Dismukes, W.E. 2000. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin. Infect. Dis.30, 710–718.
92. Sorrell, T.C., Juillard, P.G., Djordjevic, J.T., Kaufman-Francis, K., Dietmann, A., Milonig, A., Combes, V., and Grau, G.E. 2015. Cryptococcal transmigration across a model brain blood-barrier: evidence of the Trojan horse mechanism and differences between Cryptococcus neoformans var. grubii strain H99 and Cryptococcus gattii strain R265. Microbes Infect.18, 57–67.
93. Subramaniam, K., Metzger, B., Hanau, L.H., Guh, A., Rucker, L., Badri, S., and Pirofski, L.A. 2009. IgM(+) memory B cell expression predicts HIV-associated cryptococcosis status. J. Infect. Dis.200, 244–251.
94. Subramaniam, K.S., Datta, K., Quintero, E., Manix, C., Marks, M.S., and Pirofski, L.A. 2010. The absence of serum IgM enhances the susceptibility of mice to pulmonary challenge with Cryptococcus neoformans. J. Immunol.184, 5755–5767.
95. Sun, J.C., Beilke, J.N., and Lanier, L.L. 2009. Adaptive immune features of natural killer cells. Nature457, 557–561.
96. Sun, D., Zhang, M., Liu, G., Wu, H., Zhu, X., Zhou, H., and Shi, M. 2015. Real-time imaging of interactions of neutrophils with Cryptococcus neoformans: a crucial role of C5a-C5aR signaling. Infect. Immun. DOI: 10.1128/IAI.01197-15.
97. Syme, R.M., Spurrell, J.C., Amankwah, E.K., Green, F.H., and Mody, C.H. 2002. Primary dendritic cells phagocytose Cryptococcus neoformans via mannose receptors and Fcgamma receptor II for presentation to T lymphocytes. Infect. Immun.70, 5972–5981.
98. Szymczak, W.A., Davis, M.J., Lundy, S.K., Dufaud, C., Olszewski, M., and Pirofski, L.A. 2013. X-linked immunodeficient mice exhibit enhanced susceptibility to Cryptococcus neoformans infection. mBio4, e00265–13.
99. Tanaka, M., Ishii, K., Nakamura, Y., Miyazato, A., Maki, A., Abe, Y., Miyasaka, T., Yamamoto, H., Akahori, Y., Fue, M., et al. 2012. Toll-like receptor 9-dependent activation of bone marrow-derived dendritic cells by URA5 DNA from Cryptococcus neoformans. Infect. Immun.80, 778–786.
100. van der Horst, C.M., Saag, M.S., Cloud, G.A., Hamill, R.J., Graybill, J.R., Sobel, J.D., Johnson, P.C., Tuazon, C.U., Kerkering, T., Moskovitz, B.L., et al. 1997. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl. J. Med.337, 15–21.
101. Vecchiarelli, A., Pietrella, D., Lupo, P., Bistoni, F., McFadden, D.C., and Casadevall, A. 2003. The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation. J. Leukoc. Biol.74, 370–378.
102. Walsh, T.J. and Gamaletsou, M.N. 2013. Treatment of fungal disease in the setting of neutropenia. Hematology Am. Soc. Hematol. Educ. Program.2013, 423–427.
103. Wiesner, D.L., Specht, C.A., Lee, C.K., Smith, K.D., Mukaremera, L., Lee, S.T., Lee, C.G., Elias, J.A., Nielsen, J.N., Boulware, D.R., et al. 2015. Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. PLoS Pathog.11, e1004701.
104. Wiseman, J.C., Ma, L.L., Marr, K.J., Jones, G.J., and Mody, C.H. 2007. Perforin-dependent cryptococcal microbicidal activity in NK cells requires PI3K-dependent ERK1/2 signaling. J. Immunol.178, 6456–6464.
105. Wozniak, K.L., Hardison, S.E., Kolls, J.K., and Wormley, F.L. 2011. Role of IL-17A on resolution of pulmonary C. neoformans infection. PLoS One6, e17204.
106. Wozniak, K.L., Kolls, J.K., and Wormley, F.L.Jr. 2012. Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by gammadelta T cells. BMC Immunol.13, 65.
107. Wozniak, K.L. and Levitz, S.M. 2008. Cryptococcus neoformans enters the endolysosomal pathway of dendritic cells and is killed by lysosomal components. Infect. Immun.76, 4764–4771.
108. Wozniak, K.L., Ravi, S., Macias, S., Young, M.L., Olszewski, M.A., Steele, C., and Wormley, F.L. 2009. Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis. PLoS One4, e6854.
109. Wozniak, K.L., Vyas, J.M., and Levitz, S.M. 2006. In vivo role of dendritic cells in a murine model of pulmonary cryptococcosis. Infect. Immun.74, 3817–3824.
110. Wu, B., Liu, H., Huang, J., Zhang, W., and Zhang, T. 2009. Pulmonary cryptococcosis in non-AIDS patients. Clin. Invest. Med.32, E70–77.
111. Yamaguchi, H., Komase, Y., Ikehara, M., Yamamoto, T., and Shinagawa, T. 2008. Disseminated cryptococcal infection with eosinophilia in a healthy person. J. Infect. Chemother.14, 319–324.
112. Yamamoto, H., Abe, Y., Miyazato, A., Tanno, D., Tanaka, M., Miyasaka, T., Ishii, K., and Kawakami, K. 2011. Cryptococcus neoformans suppresses the activation of bone marrow-derived dendritic cells stimulated with its own DNA, but not with DNA from other fungi. FEMS Immunol. Med. Microbiol.63, 363–372.
113. Yauch, L.E., Lam, J.S., and Levitz, S.M. 2006. Direct inhibition of T-cell responses by the Cryptococcus capsular polysaccharide glucuronoxylomannan. PLoS Pathog.2, e120.
114. Zaragoza, O., Rodrigues, M.L., De Jesus, M., Frases, S., Dadachova, E., and Casadevall, A. 2009. The capsule of the fungal pathogen Cryptococcus neoformans. Adv. Appl. Microbiol.68, 133–216.
115. Zhang, Y., Wang, F., Tompkins, K.C., McNamara, A., Jain, A.V., Moore, B.B., Toews, G.B., Huffnagle, G.B., and Olszewski, M.A. 2009. Robust Th1 and Th17 immunity supports pulmonary clearance but cannot prevent systemic dissemination of highly virulent Cryptococcus neoformans H99. Am. J. Pathol.175, 2489–2500.