Chapter 32 : Innate and Acquired Cellular Immunity to Fungi

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Innate and Acquired Cellular Immunity to Fungi, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap32-1.gif /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap32-2.gif


Studies with have provided a paradigm that incorporates contributions from both the fungus and the host to explain the theme of the origin and maintenance of virulence for commensals. The majority of fungi are detected and destroyed within hours by innate defense mechanisms. Thus, innate and adaptive immune responses are intimately linked and controlled by sets of molecules and receptors that act to generate the most effective form of immunity for protection against fungal pathogens. Traditionally, the innate defense mechanisms used by the host against fungi have been considered of two types, constitutive and inducible, although the recent finding that the expression of constitutive mechanisms may be regulated by toll-like receptors (TLRs) signaling highlights the interdependency of the two systems. The different impact of TLRs on the occurrence of the innate and adaptive Th immunity to fungi is consistent with the ability of each individual TLR to activate specialized antifungal effector functions on phagocytes and dendritic cells (DCs). Binding and internalization of fungi by polymorphonuclear leukocytes (PMNs) may occur through different receptors, of which CR3 and FcγR, presumably FcγRI or FcγRI, are the most effective in terms of phagocytosis and fungicidal activity. On contact with a pathogen, cells of the innate immune system release a battery of chemokines and cytokines. The therapeutic efficacy of antifungals is limited without the help of host immune reactivity. Various cytokines, including chemokines and growth factors, have proved to be beneficial in experimental and human refractory fungal infections.

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32

Key Concept Ranking

Major Histocompatibility Complex Class II
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Interface between innate and adaptive immunity to fungi. Essential to the successful removal of pathogens is the early recognition of fungi by components of the innate immune systems. These involve the complement systems, opsonins, antibodies, and specialized receptors such as TLRs expressed on NK cells and phagocytes that recognize specific fungus-derived molecular structures. Successful engagement of some of these pathways leads to an inflammatory response with destruction of the pathogen alongside the establishment of DC and T-cell and/or B-cell interactions. A well-orchestrated innate and adaptive immune response will lead to pathogen eradication and host immunity (white box). Failure to efficiently discriminate self from nonself in innate as well as adaptive immunity can lead to pathogen proliferation and ultimately to dysregulated immunity such as autoimmunity, allergy, and sepsis (dark gray box).

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

The crucial role for the IFN-γ/IDO-dependent metabolic pathway in infection. The production of IFN-γ is placed squarely at the host/pathogen interface, where IDO activation exerts a fine control over fungal morphology as well as the inductive and effector pathways of immune resistance to the fungus.

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Apidianakis, Y.,, L. G. Rahme,, J. Heitman,, F. M. Ausubel,, S. B. Calderwood, and, E. Mylonakis. 2004. Challenge of Drosophila melanogaster with Cryptococcus neoformans and role of the innate immune response. Eukaryot. Cell 3:413419.
2. Aratani, Y.,, F. Kura,, H. Watanabe,, H. Akagawa,, Y. Takano,, K. Suzuki,, M. C. Dinauer,, N. Maeda, and, H. Koyama. 2002. Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus. Med. Mycol. 40:557563.
3. Ashman, R. B. 1998. Candida albicans : pathogenesis, immunity and host defence. Res. Immunol. 149:281288.
4. Ashman, R. B., and, J. M. Papadimitriou. 1995. Production and function of cytokines in natural and acquired immunity to Candida albicans infection. Microbiol. Rev. 59:646672.
5. Babula, O.,, G. Lazdane,, J. Kroica,, W. J. Ledger, and, S. S. Witkin. 2003. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women. Clin. Infect. Dis. 37:733737.
6. Bacci, A.,, C. Montagnoli,, K. Perruccio,, S. Bozza,, R. Gaziano,, L. Pitzurra,, A. Velardi,, C. F. d’Ostiani,, J. E. Cutler, and, L. Romani. 2002. Dendritic cells pulsed with fungal RNA induce protective immunity to Candida albicans in hematopoietic transplantation. J. Immunol. 168:29042913.
7. Belanger, P. H.,, D. A. Johnston,, R. A. Fratti,, M. Zhang, and, S. G. Filler. 2002. Endocytosis of Candida albicans by vascular endothelial cells is associated with tyrosine phosphorylation of specific host cell proteins. Cell Microbiol. 4:805812.
8. 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.
9. Bellocchio, S.,, S. Moretti,, K. Perruccio,, F. Fallarino,, S. Bozza,, C. Montagnoli,, P. Mosci,, G. B. Lipford,, L. Pitzurra, and, L. Romani. 2004. TLRs govern neutrophil activity in aspergillosis. J. Immunol. 173:74067415.
10. Bozza, S.,, F. Fallarino,, L. Pitzurra,, T. Zelante,, C. Montagnoli,, S. Bellocchio,, P. Mosci,, C. Vacca,, P. Puccetti, and, L. Romani. 2004. A crucial role for tryptophan catabolism at the host/Candida albicans interface. J. Immunol. 174:29102918.
11. Bozza, S.,, R. Gaziano,, G. B. Lipford,, C. Montagnoli,, A. Bacci,, P. Di Francesco,, V. P. Kurup,, H. Wagner, and, L. Romani. 2002. Vaccination of mice against invasive aspergillosis with recombinant Aspergillus proteins and CpG oligodeoxynucleotides as adjuvants. Microbes Infect. 4:12811290.
12. Bozza, S.,, R. Gaziano,, A. Spreca,, A. Bacci,, C. Montagnoli,, P. di Francesco, and, L. Romani. 2002. Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus. J. Immunol. 168:13621371.
13. Bozza, S.,, C. Montagnoli,, R. Gaziano,, G. Rossi,, G. Nkwanyuo,, S. Bellocchio, and, L. Romani. 2004. Dendritic cell-based vaccination against opportunistic fungi. Vaccine 2:857864.
14. Bozza, S.,, K. Perruccio,, C. Montagnoli,, R. Gaziano,, S. Bellocchio,, E. Burchielli,, G. Nkwanyuo,, L. Pitzurra,, A. Velardi, and, L. Romani. 2003. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102:38073814.
15. Braedel, S.,, M. Radsak,, H. Einsele,, J. P. Latge,, A. Michan,, J. Loeffler,, Z. Haddad,, U. Grigoleit,, H. Schild, and, H. Hebart. 2004. Aspergillus fumigatus antigens activate innate immune cells via Toll-like receptors 2 and 4. Br. J. Haematol. 125:392399.
16. Brandhorst, T. T.,, M. Wuthrich,, T. Warner, and, B. Klein. 1999. Targeted gene disruption reveals an adhesin indispensable for pathogenicity of Blastomyces dermatitidis. J. Exp. Med. 189:12071216.
17. Bronte, V.,, P. Serafini,, A. Mazzoni,, D. M. Segal, and, P. Zanovello. 2003. l-Arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol. 24:302306.
18. Buentke, E., and, A. Scheynius. 2003. Dendritic cells and fungi. Apmis 111:789796.
19. Calich, V. L.,, C. A. Vaz, and, E. Burger. 1998. Immunity to Paracoccidioides brasiliensis infection. Res. Immunol. 149:407417.
20. Cambi, A.,, K. Gijzen,, J. M. de Vries,, R. Torensma,, B. Joosten,, G. J. Adema,, M. G. Netea,, B. J. Kullberg,, L. Romani, and, C. G. Figdor. 2003. The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells. Eur. J. Immunol. 33:532538.
21. Casadevall, A. 1995. Antibody immunity and invasive fungal infections. Infect. Immun. 63:42114218.
22. Chauhan, N., and, R. Calderone. 2004. Adaptation to oxidative, nutrient and pH stress by human pathogenic fungi, p. 129–166. In G. San-Blas and R. A. Calderone (ed.), Pathogenic Fungi. Host Interactions and Emerging Strategies for Control. Caister Academic Press, Wymondham, Norfolk, England.
23. Cheng, V. C.,, K. Y. Yuen,, W. M. Chan,, S. S. Wong,, E. S. Ma, and, R. M. Chan. 2000. Immunorestitution disease involving the innate and adaptive response. Clin. Infect. Dis. 30:882892.
24. Chiani, P.,, C. Bromuro, and, A. Torosantucci. 2000. Defective induction of interleukin-12 in human monocytes by germ-tube forms of Candida albicans. Infect. Immun. 68:56285634.
25. Choi, E. H.,, C. B. Foster,, J. G. Taylor,, H. C. Erichsen,, R. A. Chen,, T. J. Walsh,, V. J. Anttila,, T. Ruutu,, A. Palotie, and, S. J. Chanock. 2003. Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J. Infect. Dis. 187:11531156.
26. Clemons, K. V., and, D. A. Stevens. 2001. Overview of host defense mechanisms in systemic mycoses and the basis for immunotherapy. Semin. Respir. Infect. 16:6066.
27. Cutuli, M.,, S. Cristiani,, J. M. Lipton, and, A. Catania. 2000. Antimicrobial effects of alpha-MSH peptides. J. Leukoc. Biol. 67:233239.
28. Deepe, G. S., Jr., and, R. S. Gibbons. 2002. Functional properties of the T cell receptor repertoire in responding to the protective domain of heat-shock protein 60 from Histoplasma capsulatum. J. Infect. Dis. 186:815822.
29. Deepe, G. S., Jr. 2004. Preventative and therapeutic vaccines for fungal infections: from concept to implementation. Expert Rev. Vaccines 3:701709.
30. Dinauer, M. C.,, M. A. Gifford,, N. Pech,, L. L. Li, and, P. Emshwiller. 2001. Variable correction of host defense following gene transfer and bone marrow transplantation in murine X-linked chronic granulomatous disease. Blood 97:37383745.
31. Dorschner, R. A.,, B. Lopez-Garcia,, J. Massie,, C. Kim, and, R. L. Gallo. 2004. Innate immune defense of the nail unit by antimicrobial peptides. J. Am. Acad. Dermatol. 50:343348.
32. Dunphy, G. B.,, U. Oberholzer,, M. Whiteway,, R. J. Zakarian, and, I. Boomer. 2003. Virulence of Candida albicans mutants toward larval Galleria mellonella (Insecta, Lepidoptera, Galleridae). Can. J. Microbiol. 49:514524.
33. Edwards, L.,, A. E. Williams,, A. M. Krieg,, A. J. Rae,, R. J. Snelgrove, and, T. Hussell. 2004. Stimulation via Toll-like receptor 9 reduces Cryptococcus neoformans- induced pulmonary inflammation in an IL-12-dependent manner. Eur. J. Immunol. 35:273281.
34. Ehlers, M. R. 2000. CR3: a general purpose adhesion-recognition receptor essential for innate immunity. Microbes Infect. 2:289294.
35. Ellerbroek, P. M.,, D. J. Lefeber,, R. van Veghel,, J. Scharringa,, E. Brouwer,, G. J. Gerwig,, G. Janbon,, A. I. Hoepelman, and, F. E. Coenjaerts. 2004. O-acetylation of cryptococcal capsular glucuronoxylomannan is essential for interference with neutrophil migration. J. Immunol. 173:75137520.
36. Ezekowitz, R. A.,, D. J. Williams,, H. Koziel,, M. Y. Armstrong,, A. Warner,, F. F. Richards, and, R. M. Rose. 1991. Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor. Nature 351:155158.
37. Feldmesser, M.,, S. Tucker, and, A. Casadevall. 2001. Intracellular parasitism of macrophages by Cryptococcus neoformans. Trends Microbiol. 9:273278.
38. Ferreira, K. S.,, J. D. Lopes, and, S. R. Almeida. 2003. Regulation of T helper cell differentiation in vivo by GP43 from Paracoccidioides brasiliensis provided by different antigen-presenting cells. Scand. J. Immunol. 58:290297.
39. Fidel, P. L., Jr. 2002. The protective immune response against vaginal candidiasis: lessons learned from clinical studies and animal models. Int. Rev. Immunol. 21:515548.
40. Franzblau, M. J. 2003. Preventing fungal infections in chronic granulomatous disease. N. Engl. J. Med. 349:11901191.
41. Garlanda, C.,, E. Hirsch,, S. Bozza,, A. Salustri,, M. De Acetis,, R. Nota,, A. Maccagno,, F. Riva,, B. Bottazzi,, G. Peri,, A. Doni,, L. Vago,, M. Botto,, R. De Santis,, P. Carminati,, G. Siracusa,, F. Altruda,, A. Vecchi,, L. Romani, and, A. Mantovani. 2002. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:182186.
42. Ghannoum, M. A. 2000. Potential role of phospholipases in virulence and fungal pathogenesis. Clin. Microbiol. Rev. 13:122143.
43. Gildea, L. A.,, R. E. Morris, and, S. L. Newman. 2001. Histoplasma capsulatum yeasts are phagocytosed via very late antigen-5, killed, and processed for antigen presentation by human dendritic cells. J. Immunol. 166:10491056.
44. Gordon, S. 2002. Pattern recognition receptors: doubling up for the innate immune response. Cell 111:927930.
45. Gow, N. A.,, A. J. Brown, and, F. C. Odds. 2002. Fungal morphogenesis and host invasion. Curr. Opin. Microbiol. 5:366371.
46. Grazziutti, M.,, D. Przepiorka,, J. H. Rex,, I. Braunschweig,, S. Vadhan-Raj, and, C. A. Savary. 2001. Dendritic cell-mediated stimulation of the in vitro lymphocyte response to Aspergillus. Bone Marrow Transplant. 27:647652.
47. Grohmann, U.,, F. Fallarino, and, P. Puccetti. 2003. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol. 24:242248.
48. Hage, C. A.,, M. Goldman, and, L. J. Wheat. 2002. Mucosal and invasive fungal infections in HIV/AIDS. Eur. J. Med. Res. 7:236241.
49. Hage, C. A.,, K. L. Wood,, H. T. Winer-Muram,, S. J. Wilson,, G. Sarosi, and, K. S. Knox. 2003. Pulmonary cryptococcosis after initiation of anti-tumor necrosis factor-alpha therapy. Chest 124:23952397.
50. Hamilton, A. J., and, M. D. Holdom. 1999. Antioxidant systems in the pathogenic fungi of man and their role in virulence. Med. Mycol. 37:375389.
51. Han, Y.,, T. R. Kozel,, M. X. Zhang,, R. S. MacGill,, M. C. Carroll, and, J. E. Cutler. 2001. Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis. J. Immunol. 167:15501557.
52. Hebart, H.,, C. Bollinger,, P. Fisch,, J. Sarfati,, C. Meisner,, M. Baur,, J. Loeffler,, M. Monod,, J. P. Latge, and, H. Einsele. 2002. Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies. Blood 100:45214528.
53. Herring, A. C., and, G. B. Huffnagle. 2001. Innate immunity to fungi, p. 127–137. In S. H. E Kaufmann, A. Sher, and R. Ahmed (ed.), Immunology of Infectious Diseases. ASM Press, Washington, D.C.
54. Hoffmann, J. A., and, J. M. Reichhart. 2002. Drosophila innate immunity: an evolutionary perspective. Nat. Immunol. 3:121126.
55. Hori, S.,, T. L. Carvalho, and, J. Demengeot. 2002. CD25+ CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. Eur. J. Immunol. 32:12821291.
56. Howard, D. H. 1999. Acquisition, transport, and storage of iron by pathogenic fungi. Clin. Microbiol. Rev. 12:394404.
57. 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.
58. Ibata-Ombetta, S.,, T. Idziorek,, P. A. Trinel,, D. Poulain, and, T. Jouault. 2003. Candida albicans phospholipomannan promotes survival of phagocytosed yeasts through modulation of bad phosphorylation and macrophage apoptosis. J. Biol. Chem. 278:1308613093.
59. Kaposzta, R.,, L. Marodi,, M. Hollinshead,, S. Gordon, and, R. P. da Silva. 1999. Rapid recruitment of late endosomes and lysosomes in mouse macrophages ingesting Candida albicans. J. Cell Sci. 112:32373248.
60. Kawakami, K. 2003. Promising immunotherapies with Th1-related cytokines against infectious diseases. J. Infect. Chemother. 9:201209.
61. Kawakami, K. 2004. Regulation by innate immune T lymphocytes in the host defense against pulmonary infection with Cryptococcus neoformans. Jpn. J. Infect. Dis. 57:137145.
62. Kawakami, K. 2002. Role of natural killer T cells in host defence against cryptococcal infection. Rev. Iberoam. Micol. 19:149154.
63. Kelly, R. M.,, J. Chen,, L. E. Yauch, and, S. M. Levitz. 2005. Opsonic requirements for dendritic cell-mediated responses to Cryptococcus neoformans. Infect. Immun. 73:592598.
64. Koguchi, Y., and, K. Kawakami. 2002. Cryptococcal infection and Th1-Th2 cytokine balance. Int. Rev. Immunol. 21:423438.
65. Kottom, T. J.,, J. R. Kohler,, C. F. Thomas, Jr.,, G. R. Fink, and, A. H. Limper. 2003. Lung epithelial cells and extracellular matrix components induce expression of Pneumocystis carinii STE20, a gene complementing the mating and pseudohyphal growth defects of STE20 mutant yeast. Infect. Immun. 71:64636471.
66. Kozel, T. R. 1998. Complement activation by pathogenic fungi. Res. Immunol. 149:309320.
67. Kullberg, B. J.,, A. M. Oude Lashof, and, M. G. Netea. 2004. Design of efficacy trials of cytokines in combination with antifungal drugs. Clin. Infect. Dis. 39:218223.
68. Lasbury, M. E.,, X. Tang,, P. J. Durant, and, C. H. Lee. 2003. Effect of transcription factor GATA-2 on phagocytic activity of alveolar macrophages from Pneumocystis carinii-infected hosts. Infect. Immun. 71:49434952.
69. Latge, J. P. 2001. The pathobiology of Aspergillus fumigatus. Trends Microbiol. 9:382389.
70. Levitz, S. M. 2004. Interactions of Toll-like receptors with fungi. Microbes Infect. 6:13511355.
71. Levitz, S. M.,, H. L. Mathews, and, J. W. Murphy. 1995. Direct antimicrobial activity of T cells. Immunol. Today 16:387391.
72. Lilic, D. 2002. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr. Opin. Infect. Dis. 15:143147.
73. Lilic, D.,, I. Gravenor,, N. Robson,, D. A. Lammas,, P. Drysdale,, J. E. Calvert,, A. J. Cant, and, M. Abinun. 2003. Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis. Infect. Immun. 71:56905699.
74. Liston, A.,, S. Lesage,, J. Wilson,, L. Peltonen, and, C. C. Goodnow. 2003. Aire regulates negative selection of organ-specific T cells. Nat. Immunol. 4:350354.
75. Liu, L.,, K. Kang,, M. Takahara,, K. D. Cooper, and, M. A. Ghannoum. 2001. Hyphae and yeasts of Candida albi-cans differentially regulate interleukin-12 production by human blood monocytes: inhibitory role of C. albicans germination. Infect. Immun. 69:46954697.
76. Long, K. H.,, F. J. Gomez,, R. E. Morris, and, S. L. Newman. 2003. Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J. Immunol. 170:487494.
77. Lopes Bezerra, L. M., and, S. G. Filler. 2004. Interactions of Aspergillus fumigatus with endothelial cells: internalization, injury, and stimulation of tissue factor activity. Blood 103:21432149.
78. Lorenz, M. C., and, G. R. Fink. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412:8386.
79. 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.
80. Magee, D. M., and, R. A. Cox. 2002. Cell-mediated immunity and endemic mycoses, p. 279–292. In R. A. Calderone and R. L. Cihlar (ed.), Fungal Pathogenesis: Principles and Clinical Applications. Marcel Dekker, Inc., New York, N.Y.
81. Mansour, M. K., and, S. M. Levitz. 2002. Interactions of fungi with phagocytes. Curr. Opin. Microbiol. 5:359365.
82. Marodi, L.,, S. Schreiber,, D. C. Anderson,, R. P. MacDermott,, H. M. Korchak, and, R. B. Johnston, Jr. 1993. Enhancement of macrophage candidacidal activity by interferon-gamma. Increased phagocytosis, killing, and calcium signal mediated by a decreased number of mannose receptors. J. Clin. Investig. 91:25962601.
83. Marr, K. A.,, R. A. Carter,, M. Boeckh,, P. Martin, and, L. Corey. 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100:43584366.
84. McCormack, F. X., and, J. A. Whitsett. 2002. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J. Clin. Investig. 109:707712.
85. McKnight, A. J., and, S. Gordon. 2000. Forum in immunology: innate recognition systems. Microbes Infect. 2:239336.
86. Mencacci, A.,, C. Montagnoli,, A. Bacci,, E. Cenci,, L. Pitzurra,, A. Spreca,, M. Kopf,, A. H. Sharpe, and, L. Romani. 2002. CD80+ Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis. J. Immunol. 169:31803190.
87. Montagnoli, C.,, A. Bacci,, S. Bozza,, R. Gaziano,, S. Fiorucci,, A. Spreca, and, L. Romani. 2001. The plasticity of dendritic cells at the host/fungal interface. Immunobiology 204:582589.
88. Montagnoli, C.,, A. Bacci,, S. Bozza,, R. Gaziano,, P. Mosci,, A. H. Sharpe, and, L. Romani. 2002. B7/CD28-dependent CD4+ CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J. Immunol. 169:62986308.
89. Montagnoli, C.,, S. Bozza,, A. Bacci,, R. Gaziano,, P. Mosci,, J. Morschhauser,, L. Pitzurra,, M. Kopf,, J. Cutler, and, L. Romani. 2003. A role for antibodies in the generation of memory antifungal immunity. Eur. J. Immunol. 33:11931204.
90. Murphy, J. W. 1989. Immunity to fungi. Curr. Opin. Immunol. 2:360367.
91. Netea, M. G.,, P. M. Schneeberger,, E. de Vries,, B. J. Kullberg,, J. W. van der Meer, and, M. I. Koolen. 2002. Th1/Th2 cytokine imbalance in a family with hyper-IgE syndrome. Neth. J. Med. 60:349353.
92. Netea, M. G.,, R. J. Stuyt,, S. H. Kim,, J. W. Van der Meer,, B. J. Kullberg, and, C. A. Dinarello. 2002. The role of endogenous interleukin (IL)-18, IL-12, IL-1beta, and tumor necrosis factor-alpha in the production of inter-feron-gamma induced by Candida albicans in human whole-blood cultures. J. Infect. Dis. 185:963970.
93. Netea, M. G.,, C. A. Van Der Graaf,, A. G. Vonk,, I. Verschueren,, J. W. Van Der Meer, and, B. J. Kullberg. 2002. The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J. Infect. Dis. 185:14831489.
94. Netea, M. G.,, J. W. Van der Meer, and, B. J. Kullberg. 2004. Toll-like receptors as an escape mechanism from the host defense. Trends Microbiol. 12:484488.
95. Netea, M. G.,, A. Warris,, J. W. Van der Meer,, M. J. Fenton,, T. J. Verver-Janssen,, L. E. Jacobs,, T. Andresen,, P. E. Verweij, and, B. J. Kullberg. 2003. Aspergillus fumigatus evades immune recognition during germination through loss of Toll-like receptor-4-mediated signal transduction. J. Infect. Dis. 188:320326.
96. Neth, O.,, D. L. Jack,, A. W. Dodds,, H. Holzel,, N. J. Klein, and, M. W. Turner. 2000. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect. Immun. 68:688693.
97. Newman, S. L., and, A. Holly. 2001. Candida albicans is phagocytosed, killed, and processed for antigen presentation by human dendritic cells. Infect. Immun. 69:68136822.
98. O’Neill, L. A.,, K. A. Fitzgerald, and, A. G. Bowie. 2003. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 24:286290.
99. Pasare, C., and, R. Medzhitov. 2003. Toll pathway-dependent blockade of CD4+ CD25+ T cell-mediated suppression by dendritic cells. Science 299:10331036.
100. Phan, Q. T.,, R. A. Fratti,, N. V. Prasadarao,, J. E. Edwards, Jr., and, S. G. Filler. 2005. N-cadherin mediates endocytosis of Candida albicans by endothelial cells. J. Biol. Chem. 280:1045510461.
101. Poulain, D., and, T. Jouault. 2004. Candida albicans cell wall glycans, host receptors and responses: elements for a decisive crosstalk. Curr. Opin. Microbiol. 7:342349.
102. Puccetti, P.,, L. Romani, and, F. Bistoni. 1995. A TH1-TH2-like switch in candidiasis: new perspectives for therapy. Trends Microbiol. 3:237240.
103. Reis e Sousa, C.,, A. Sher, and, P. Kaye. 1999. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr. Opin. Immunol. 11:392399.
104. Richards, J. O.,, N. M. Ampel, and, D. F. Lake. 2002. Reversal of coccidioidal anergy in vitro by dendritic cells from patients with disseminated coccidioidomycosis. J. Immunol. 169:20202025.
105. Roeder, A.,, C. J. Kirschning,, R. A. Rupec,, M. Schaller, and, H. C. Korting. 2004. Toll-like receptors and innate antifungal responses. Trends Microbiol. 12:4449.
106. Romani, L. 2004. Innate immunity to fungi: the art of speed and specificity, p. 167–214. In G. San-Blas and R. A. Calderone (ed.), Pathogenic Fungi. Host Interactions and Emerging Strategies for Control. Caister Academic Press, Wymondham, Norfolk, England.
107. Romani, L. 2001. Overview of the fungal pathogens, p. 25–37. In S. H. E Kaufmann, A. Sher, and R. Ahmed (ed.), Immunology of Infectious Diseases. ASM Press, Washington, D.C.
108. Romani, L. 2001. Host immune reactivity and antifungal chemotherapy: the power of being together. J. Chemother. 13:347353.
109. Romani, L. 2004. Immunity to fungal infections. Nat. Rev. Immunol. 4:123.
110. Romani, L. 1997. The T cell response against fungal infections. Curr. Opin. Immunol. 9:484490.
111. Romani, L.,, F. Bistoni,, R. Gaziano,, S. Bozza,, C. Montagnoli,, K. Perruccio,, L. Pitzurra,, S. Bellocchio,, A. Velardi,, G. Rasi,, P. Di Francesco, and, E. Garaci. 2004. Thymosin alpha 1 activates dendritic cells for anti-fungal Th1 resistance through Toll-like receptor signaling. Blood 103:42324239.
112. Romani, L.,, F. Bistoni, and, P. Puccetti. 2002. Fungi, dendritic cells and receptors: a host perspective of fungal virulence. Trends Microbiol. 10:508514.
113. Romani, L., and, S. H. Kaufmann. 1998. Immunity to fungi: editorial overview. Res. Immunol. 149:277281.
114. 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.
115. Rooney, P. J., and, B. S. Klein. 2002. Linking fungal morphogenesis with virulence. Cell. Microbiol. 4:127137.
116. Rubin-Bejerano, I.,, I. Fraser,, P. Grisafi, and, G. R. Fink. 2003. Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans. Proc. Natl. Acad. Sci. USA 100:1100711012.
117. Schaffner, A.,, H. Douglas, and, A. Braude. 1982. Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J. Clin. Investig. 69:617631.
118. Schofield, D. A.,, C. Westwater, and, E. Balish. 2004. Beta-defensin expression in immunocompetent and immunodeficient germ-free and Candida albicans- monoassociated mice. J. Infect. Dis. 190:13271334.
119. Schroppel, K.,, M. Kryk,, M. Herrmann,, E. Leberer,, M. Rollinghoff, and, C. Bogdan. 2001. Suppression of type 2 NO-synthase activity in macrophages by Candida albicans. Int. J. Med. Microbiol. 290:659668.
120. Serrano-Gomez, D.,, A. Dominguez-Soto,, J. Ancochea,, J. A. Jimenez-Heffernan,, J. A. Leal, and, A. L. Corbi. 2004. Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages. J. Immunol. 173:56355643.
121. Shoham, S.,, C. Huang,, J. M. Chen,, D. T. Golenbock, and, S. M. Levitz. 2001. Toll-like receptor 4 mediates intracellular signaling without TNF-alpha release in response to Cryptococcus neoformans polysaccharide capsule. J. Immunol. 166:46204626.
122. Steele, C.,, L. Marrero,, S. Swain,, A. G. Harmsen,, M. Zheng,, G. D. Brown,, S. Gordon,, J. E. Shellito, and, J. K. Kolls. 2003. Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor. J. Exp. Med. 198:16771688.
123. Syme, R. M.,, J. C. Spurrell,, E. K. Amankwah,, F. H. Green, and, C. H. Mody. 2002. Primary dendritic cells phagocytose Cryptococcus neoformans via mannose receptors and Fcγ receptor II for presentation to T lymphocytes. Infect. Immun. 70:59725981.
124. Tada, H.,, E. Nemoto,, H. Shimauchi,, T. Watanabe,, T. Mikami,, T. Matsumoto,, N. Ohno,, H. Tamura,, K. Shibata,, S. Akashi,, K. Miyake,, S. Sugawara, and, H. Takada. 2002. Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like receptor 4-dependent manner. Microbiol. Immunol. 46:503512.
125. Torosantucci, A.,, P. Chiani,, F. De Bernardis,, A. Cassone,, J. A. Calera, and, R. Calderone. 2002. Deletion of the two-component histidine kinase gene (CHK1) of Candida albicans contributes to enhanced growth inhibition and killing by human neutrophils in vitro. Infect. Immun. 70:985987.
126. Torosantucci, A.,, G. Romagnoli,, P. Chiani,, A. Stringaro,, P. Crateri,, S. Mariotti,, R. Teloni,, G. Arancia,, A. Cassone, and, R. Nisini. 2004. Candida albicans yeast and germ tube forms interfere differently with human monocyte differentiation into dendritic cells: a novel dimorphism-dependent mechanism to escape the host’s immune response. Infect. Immun. 72:833843.
127. Turner, M. W. 1996. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol. Today 17:532540.
128. 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.
129. van Spriel, A. B.,, I. E. van den Herik-Oudijk,, N. M. van Sorge,, H. A. Vile,, J. A. van Strijp, and, J. G. van de Winkel. 1999. Effective phagocytosis and killing of Candida albicans via targeting FcγRI (CD64) or FcγRI (CD89) on neutrophils. J. Infect. Dis. 179:661669.
130. Vora, P.,, A. Youdim,, L. S. Thomas,, M. Fukata,, S. Y. Tesfay,, K. Lukasek,, K. S. Michelsen,, A. Wada,, T. Hirayama,, M. Arditi, and, M. T. Abreu. 2004. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol. 173:53985405.
131. Wang, J. E.,, A. Warris,, E. A. Ellingsen,, P. F. Jorgensen,, T. H. Flo,, T. Espevik,, R. Solberg,, P. E. Verweij, and, A. O. Aasen. 2001. Involvement of CD14 and Toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae. Infect. Immun. 69:24022406.
132. Warris, A.,, A. Bjorneklett, and, P. Gaustad. 2001. Invasive pulmonary aspergillosis associated with infliximab therapy. N. Engl. J. Med. 344:10991100.
133. Wasylnka, J. A., and, M. M. Moore. 2003. Aspergillus fumigatus conidia survive and germinate in acidic organelles of A549 epithelial cells. J. Cell Sci. 116:15791587.
134. Weber, S. M.,, S. M. Levitz, and, T. S. Harrison. 2000. Chloroquine and the fungal phagosome. Curr. Opin. Microbiol. 3:349353.
135. Wood, K. L.,, C. A. Hage,, K. S. Knox,, M. B. Kleiman,, A. Sannuti,, R. B. Day,, L. J. Wheat, and, H. L. Twigg, 3rd. 2003. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am. J. Respir. Crit. Care Med. 167:12791282.
136. Woods, J. P. 2003. Knocking on the right door and making a comfortable home: Histoplasma capsulatum intracellular pathogenesis. Curr. Opin. Microbiol. 6:327331.
137. 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.
138. Wuthrich, M.,, H. I. Filutowicz,, T. Warner, and, B. S. Klein. 2002. Requisite elements in vaccine immunity to Blastomyces dermatitidis: plasticity uncovers vaccine potential in immune-deficient hosts. J. Immunol. 169:69696976.
139. Xu, M.,, Z. Wang, and, R. M. Locksley. 2004. Innate immune responses in peptidoglycan recognition protein L-deficient mice. Mol. Cell. Biol. 24:79497957.
140. Yamamoto, M.,, S. Sato,, H. Hemmi,, K. Hoshino,, T. Kaisho,, H. Sanjo,, O. Takeuchi,, M. Sugiyama,, M. Okabe,, K. Takeda, and, S. Akira. 2003. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640643.
141. Yauch, L. E.,, M. K. Mansour,, S. Shoham,, J. B. Rottman, and, S. M. Levitz. 2004. Involvement of CD14, Toll-like receptors 2 and 4, and MyD88 in the host response to the fungal pathogen Cryptococcus neoformans in vivo. Infect. Immun. 72:53735382.


Generic image for table
Table 1.

Functional plasticity of DCs at the fungus/immune system interface

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error