Hostname: page-component-76fb5796d-45l2p Total loading time: 0 Render date: 2024-04-25T16:46:53.394Z Has data issue: false hasContentIssue false

Immune defence mechanisms and immunoenhancement strategies in oropharyngeal candidiasis

Published online by Cambridge University Press:  13 October 2008

Cristina Cunha Villar*
Affiliation:
Department of Periodontics, University of Texas Health Science Center at San Antonio School of Dentistry, San Antonio, Texas, USA.
Anna Dongari-Bagtzoglou
Affiliation:
Division of Periodontology, School of Dental Medicine, University of Connecticut, Farmington, USA.
*
*Corresponding author: Cristina Cunha Villar, Department of Periodontics, University of Texas Health Science Center at San Antonio, School of Dentistry, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Tel: +1 210 567 3600; Fax: +1 210 567 6858; E-mail: villar@uthscsa.edu

Abstract

The prevalence of oropharyngeal candidiasis continues to be high, mainly because of an increasing population of immunocompromised patients. Traditional treatment of oropharyngeal candidiasis has relied on the use of antimicrobial drugs. However, unsatisfactory results with drug monotherapy and the emergence of resistant strains have prompted investigations into the potential use of adjunctive immunoenhancing therapies for the treatment of these infections. Here we review the host-recognition systems of Candida albicans, the immune and inflammatory response to infection, and antifungal effector mechanisms. The potential of immune modulation as a therapeutic strategy in oropharyngeal candidiasis is also discussed.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Odds, F.C. (1988) Candida and candidiasis. Balliere Tindall, LondonGoogle Scholar
2Scully, C., el Kabir, M. and Samaranayake, L.P (1994) Candida and oral candidiasis: A review. Crit Rev Oral Biol Med 5, 125-157CrossRefGoogle ScholarPubMed
3Rubin, R.H. (1993) Fungal and bacterial infections in the immunocompromised host. Eur J Clin Microbiol Infect Dis 12, S42-48CrossRefGoogle ScholarPubMed
4Ohmit, S.E. et al. (2003) Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. J Infect Dis 188, 118-127CrossRefGoogle ScholarPubMed
5Redding, S.W. et al. (1999) Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer. J Clin Microbiol 37, 3896-3900CrossRefGoogle ScholarPubMed
6Hermann, P. et al. (2005) Incidence of oropharyngeal candidosis in stem cell transplant (SCT) patients. Acta Microbiol Immunol Hung 52, 85-94CrossRefGoogle ScholarPubMed
7Penk, A. and Pittrow, L. (1999) Therapeutic experience with fluconazole in the treatment of fungal infections in diabetic patients. Mycoses 42 (Suppl. 2), 97-100CrossRefGoogle ScholarPubMed
8Neville, B.W. et al. (2002) Oral and Maxillofacial Pathology, 2nd edn. Saunders, PhiladelphiaGoogle Scholar
9Anaissie, E.J. and Bodey, G.P. (1990) Fungal infections in patients with cancer. Pharmacotherapy 10, 164S-169SCrossRefGoogle ScholarPubMed
10Richet, H.M. et al. (1991) Risk factors for candidemia in patients with acute lymphocytic leukemia. Rev Infect Dis 13, 211-215CrossRefGoogle ScholarPubMed
11Samonis, G. and Bafaloukos, D. (1992) Fungal infections in cancer patients: an escalating problem. In Vivo 6, 183-193Google ScholarPubMed
12Mukhopadhyay, S. et al. (2004) The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology 112, 521-530CrossRefGoogle ScholarPubMed
13Brown, G.D. et al. (2003) Dectin-1 mediates the biological effects of β-glucans. J Exp Med 197, 1119-1124CrossRefGoogle ScholarPubMed
14Forsyth, C.B., Plow, E.F. and Zhang, L. (1998) Interaction of the fungal pathogen Candida albicans with integrin CD11b/CD18: recognition by the I domain is modulated by the lectin-like domain and the CD18 subunit. J Immunol 161, 6198-6205CrossRefGoogle ScholarPubMed
15Underhill, D.M. et al. (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401, 811-815CrossRefGoogle ScholarPubMed
16Takeda, K. et al. (2003) Toll-like receptors. Annu Rev Immunol 21, 335-376CrossRefGoogle ScholarPubMed
17Janeway, C.A. and Medzhitov, R. (2002) Innate immune recognition. Annu Rev Immunol 20, 197-216CrossRefGoogle ScholarPubMed
18Roeder, A. et al. (2004) Toll-like receptors and innate antifungal responses. Trends Microbiol 12, 44-49CrossRefGoogle ScholarPubMed
19Bellocchio, S. et al. (2004) The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol 172, 3059-3069CrossRefGoogle ScholarPubMed
20Gozalbo, D. et al. (2004) Candida and candidiasis: the cell wall as a potential molecular target for antifungal therapy. Curr Drug Targets Infect Disord 4, 117-135CrossRefGoogle ScholarPubMed
21Marr, K.A. et al. (2003) Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens. Infect Immun 71, 5280-5286CrossRefGoogle ScholarPubMed
22Netea, M.G. et al. (2002) The role of Toll-like receptors in the defense against disseminated candidiasis. J Infect Dis 185, 1483-1489CrossRefGoogle ScholarPubMed
23Villamon, E. et al. (2004) Toll-like receptor-2 is essential in murine defenses against Candida albicans infections. Microbes Infect 6, 1-7CrossRefGoogle ScholarPubMed
24Netea, M.G. et al. (2004) Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol 3712-3718CrossRefGoogle ScholarPubMed
25Murciano, C. et al. (2006) Toll-like receptor 4 defective mice carrying point or null mutations do not show increased susceptibility to Candida albicans in a model of hematogenously disseminated infection. Med Mycol 44, 149-157CrossRefGoogle ScholarPubMed
26Fidel, P.L. Jr. (2002) Distinct protective host defenses against oral and vaginal candidiasis. Med Mycol 40, 359-375CrossRefGoogle ScholarPubMed
27Romani, L. (1999) Immunity to Candida albicans: Th1, Th2 cells and beyond. Curr Opin Microbiol 2, 363-367CrossRefGoogle ScholarPubMed
28Fidel, P.L. Jr. (2002) Immunity to Candida. Oral Dis 8 (Suppl. 2), 69-75CrossRefGoogle ScholarPubMed
29Uehara, A., Sugawara, S. and Takada, H. (2002) Priming of human oral epithelial cells by interferon-gamma to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans. J Med Microbiol 51, 626-634CrossRefGoogle ScholarPubMed
30Hayashi, F., Means, T.K. and Luster, A.D. (2003) Toll-like receptors stimulate human neutrophil function. Blood 102, 2660-2669CrossRefGoogle ScholarPubMed
31Cottalorda, A. et al. (2006) TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation. Eur J Immunol 36, 1684-1693CrossRefGoogle ScholarPubMed
32Mahanonda, R. and Pichyangkul, S. (2007) Toll-like receptors and their role in periodontal health and disease. Periodontol 2000 43, 41-55CrossRefGoogle ScholarPubMed
33Pivarcsi, A. et al. (2003) Expression and function of Toll-like receptors 2 and 4 in human keratinocytes. Int Immunol 15, 721-730CrossRefGoogle ScholarPubMed
34Weindl, G. et al. (2007) Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J Clin Invest 117, 3664-3672Google ScholarPubMed
35Netea, M.G. et al. (2006) Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J Clin Invest 116, 1642-1650CrossRefGoogle ScholarPubMed
36Marodi, L., Forehand, J.R. and Johnston, R.B. Jr. (1991) Mechanisms of host defense against Candida species. II. Biochemical basis for the killing of Candida by mononuclear phagocytes. J Immunol 146, 2790-2794CrossRefGoogle ScholarPubMed
37Marodi, L., Korchak, H.M. and Johnston, R.B. Jr. (1991) Mechanisms of host defense against Candida species. I. Phagocytosis by monocytes and monocyte-derived macrophages. J Immunol 146, 2783-2789CrossRefGoogle ScholarPubMed
38Yamamoto, Y., Klein, T.W. and Friedman, H. (1997) Involvement of mannose receptor in cytokine interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor responses, but not in chemokine macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC responses, caused by attachment of Candida albicans to macrophages. Infect Immun 65, 1077-1082CrossRefGoogle Scholar
39Romani, L. et al. (2004) The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicans. Int Immunol 16, 149-161CrossRefGoogle ScholarPubMed
40Dobozy, A. et al. (1996) Mannose receptors are implicated in the Candida albicans killing activity of epidermal cells. Acta Microbiol Immunol Hung 43, 93-95Google ScholarPubMed
41Szolnoky, G. et al. (2001) A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans. J Invest Dermatol 117, 205-213CrossRefGoogle ScholarPubMed
42Lee, S.J. et al. (2003) Normal host defense during systemic candidiasis in mannose receptor-deficient mice. Infect Immun 71, 437-445CrossRefGoogle ScholarPubMed
43Brown, G.D. (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol 6, 33-43CrossRefGoogle ScholarPubMed
44Brown, G.D. and Gordon, S. (2001) Immune recognition. A new receptor for beta-glucans. Nature 413, 36-37CrossRefGoogle ScholarPubMed
45Gantner, B.N., Simmons, R.M. and Underhill, D.M. (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24, 1277-1286CrossRefGoogle Scholar
46Dongari-Bagtzoglou, A. (2008) Pathogenesis of mucosal biofilm infections: challenges and progress. Expert Rev Anti Infect Ther 6, 201-208CrossRefGoogle ScholarPubMed
47Gow, N.A. et al. (2007) Immune recognition of Candida albicans beta-glucan by dectin-1. J Infect Dis 196, 1565-1571CrossRefGoogle ScholarPubMed
48Suram, S. et al. (2006) Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the beta-glucan receptor. J Biol Chem 281, 5506-5514CrossRefGoogle ScholarPubMed
49Kennedy, A.D. et al. (2007) Dectin-1 promotes fungicidal activity of human neutrophils. Eur J Immunol 37, 467-478CrossRefGoogle ScholarPubMed
50Rogers, N.C. et al. (2005) Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22, 507-517CrossRefGoogle ScholarPubMed
51Gantner, B.N. et al. (2003) Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med 197, 1107-1117CrossRefGoogle ScholarPubMed
52Taylor, P.R. et al. (2007) Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol 8, 31-38CrossRefGoogle ScholarPubMed
53Saijo, S. et al. (2007) Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 8, 39-46CrossRefGoogle Scholar
54Cambi, A. et al. (2003) The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells. Eur J Immunol 33, 532-538CrossRefGoogle ScholarPubMed
55Taylor, P.R. et al. (2004) The role of SIGNR1 and the beta-glucan receptor (dectin-1) in the nonopsonic recognition of yeast by specific macrophages. J Immunol 172, 1157-1162CrossRefGoogle ScholarPubMed
56O'Neill, L.A. et al. (2003) Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors. J Endotoxin Res 9, 55-59CrossRefGoogle Scholar
57Villamon, E. et al. (2004) Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida-induced production of cytokines. Eur Cytokine Netw 15, 263-271Google ScholarPubMed
58Netea, M.G. et al. (2006) Recognition of fungal pathogens by toll-like receptors. Curr Pharm Des 12, 4195-4201CrossRefGoogle ScholarPubMed
59Saville, S.P. et al. (2003) Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot Cell 2, 1053-1060CrossRefGoogle ScholarPubMed
60Mathieson, R. and Dutta, S.K. (1983) Candida esophagitis. Dig Dis Sci 28, 365-370CrossRefGoogle ScholarPubMed
61Netea, M.G. et al. (2008) An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol 6, 67-78CrossRefGoogle ScholarPubMed
62van der Graaf, C.A. et al. (2005) Differential cytokine production and Toll-like receptor signaling pathways by Candida albicans blastoconidia and hyphae. Infect Immun 73, 7458-7464CrossRefGoogle ScholarPubMed
63Lilly, E.A. et al. (2004) Tissue-associated cytokine expression in HIV-positive persons with oropharyngeal candidiasis. J Infect Dis 190, 605-612CrossRefGoogle ScholarPubMed
64Dongari-Bagtzoglou, A. and Kashleva, H. (2003) Granulocyte-macrophage colony-stimulating factor responses of oral epithelial cells to Candida albicans. Oral Microbiol Immunol 18, 165-170CrossRefGoogle ScholarPubMed
65Li, L., Kashleva, H. and Dongari-Bagtzoglou, A. (2007) Cytotoxic and cytokine-inducing properties of Candida glabrata in single and mixed oral infection models. Microb Pathog 42, 138-147CrossRefGoogle ScholarPubMed
66Li, L. and Dongari-Bagtzoglou, A. (2007) Oral epithelium-Candida glabrata interactions in vitro. Oral Microbiol Immunol 22, 182-187CrossRefGoogle ScholarPubMed
67Djeu, J.Y. et al. (1988) Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes. J Immunol 141, 4047-4052CrossRefGoogle ScholarPubMed
68Djeu, J.Y., Serbousek, D. and Blanchard, D.K. (1990) Release of tumor necrosis factor by human polymorphonuclear leukocytes. Blood 76, 1405-1409CrossRefGoogle ScholarPubMed
69Marquis, M. et al. (2006) CD8+ T cells but not polymorphonuclear leukocytes are required to limit chronic oral carriage of Candida albicans in transgenic mice expressing human immunodeficiency virus type 1. Infect Immun 74, 2382-2391CrossRefGoogle Scholar
70Romani, L. (2004) Immunity to fungal infections. Nat Rev Immunol 4, 1-23CrossRefGoogle ScholarPubMed
71Steele, C. et al. (1999) Growth inhibition of Candida albicans by vaginal cells from naive mice. Med Mycol 37, 251-259CrossRefGoogle ScholarPubMed
72Steele, C. et al. (2000) Growth inhibition of Candida by human oral epithelial cells. J Infect Dis 182, 1479-1485CrossRefGoogle ScholarPubMed
73Fidel, P.L. Jr. et al. (1999) Analysis of vaginal cell populations during experimental vaginal candidiasis. Infect Immun 67, 3135-3140CrossRefGoogle ScholarPubMed
74Farah, C.S. et al. (2001) T cells augment monocyte and neutrophil function in host resistance against oropharyngeal candidiasis. Infect Immun 69, 6110-6118CrossRefGoogle ScholarPubMed
75Marquis, M. et al. (2006) CD8+ T cells but not polymorphonuclear leukocytes are required to limit chronic oral carriage of Candida albicans in transgenic mice expressing human immunodeficiency virus type 1. Infect Immun 74, 2382-2391CrossRefGoogle Scholar
76Baggiolini, M., Walz, A. and Kunkel, S.L. (1989) Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84, 1045-1049CrossRefGoogle ScholarPubMed
77Casale, T.B. and Carolan, E.J. (1999) Combination of IL-8 plus TNF alpha induces additive neutrophil migration. Allergy Asthma Proc 20, 361-363CrossRefGoogle ScholarPubMed
78Dongari-Bagtzoglou, A., Villar, C.C. and Kashleva, H. (2005) Candida albicans-infected oral epithelial cells augment the anti-fungal activity of human neutrophils in vitro. Med Mycol 43, 545-549CrossRefGoogle ScholarPubMed
79Pereira, H.A. and Hosking, C.S. (1984) The role of complement and antibody in opsonization and intracellular killing of Candida albicans. Clin Exp Immunol 57, 307-317Google ScholarPubMed
80Richardson, M.D. and Smith, H. (1981) Resistance of virulent and attenuated strains of Candida albicans to intracellular killing by human and mouse phagocytes. J Infect Dis 144, 557-564CrossRefGoogle ScholarPubMed
81Aratani, Y. et al. (2002) Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans. J Infect Dis 185, 1833-1837CrossRefGoogle ScholarPubMed
82Diamond, R.D., Lyman, C.A. and Wysong, D.R. (1991) Disparate effects of interferon-gamma and tumor necrosis factor-alpha on early neutrophil respiratory burst and fungicidal responses to Candida albicans hyphae in vitro. J Clin Invest 87, 711-720CrossRefGoogle ScholarPubMed
83Le, J. and Vilcek, J. (1987) Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 56, 234-248Google ScholarPubMed
84Tan, A.M. et al. (1995) Activation of the neutrophil bactericidal activity for nontypable Haemophilus influenzae by tumor necrosis factor and lymphotoxin. Pediatr Res 37, 155-159CrossRefGoogle ScholarPubMed
85Gadish, M. et al. (1991) Effects of recombinant human granulocyte and granulocyte-macrophage colony-stimulating factors on neutrophil function following autologous bone marrow transplantation. Leuk Res 15, 1175-1182CrossRefGoogle ScholarPubMed
86Schroder, J.M. and Christophers, E. (1986) Identification of C5ades arg and an anionic neutrophil-activating peptide (ANAP) in psoriatic scales. J Invest Dermatol 87, 53-58CrossRefGoogle Scholar
87Djeu, J.Y. et al. (1990) Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8. J Immunol 144, 2205-2210CrossRefGoogle ScholarPubMed
88Steinbakk, M. et al. (1990) Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet 336, 763-765CrossRefGoogle ScholarPubMed
89Sohnle, P.G., Collins-Lech, C. and Wiessner, J.H. (1991) Antimicrobial activity of an abundant calcium-binding protein in the cytoplasm of human neutrophils. J Infect Dis 163, 187-192CrossRefGoogle ScholarPubMed
90Hurtrel, B. and Lagrange, P.H. (1981) Comparative effects of carrageenan on systemic candidiasis and listeriosis in mice. Clin Exp Immunol 44, 355-358Google ScholarPubMed
91Jensen, J., Warner, T. and Balish, E. (1993) Resistance of SCID mice to Candida albicans administered intravenously or colonizing the gut: role of polymorphonuclear leukocytes and macrophages. J Infect Dis 167, 912-919CrossRefGoogle ScholarPubMed
92Qian, Q. et al. (1994) Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. J Immunol 152, 5000-5008CrossRefGoogle ScholarPubMed
93Vonk, A.G. et al. (2002) Phagocytosis and intracellular killing of Candida albicans blastoconidia by neutrophils and macrophages: a comparison of different microbiological test systems. J Microbiol Methods 49, 55-62CrossRefGoogle ScholarPubMed
94Netea, M.G., Kullberg, B.J. and Van der Meer, J.W. (2004) Proinflammatory cytokines in the treatment of bacterial and fungal infections. BioDrugs 18, 9-22CrossRefGoogle ScholarPubMed
95Wellington, M., Bliss, J.M. and Haidaris, C.G. (2003) Enhanced phagocytosis of Candida species mediated by opsonization with a recombinant human antibody single-chain variable fragment. Infect Immun 71, 7228-7231CrossRefGoogle ScholarPubMed
96Wellington, M., Dolan, K. and Haidaris, C.G. (2007) Monocyte responses to Candida albicans are enhanced by antibody in cooperation with antibody-independent pathogen recognition. FEMS Immunol Med Microbiol 51, 70-83CrossRefGoogle ScholarPubMed
97Beno, D.W., Stover, A.G. and Mathews, H.L. (1995) Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes. J Immunol 157, 5273-5281CrossRefGoogle Scholar
98Farah, C.S. et al. (2002) Primary role for CD4(+) T lymphocytes in recovery from oropharyngeal candidiasis. Infect Immun 70, 724-731CrossRefGoogle ScholarPubMed
99Leigh, J.E., McNulty, K.M. and Fidel, P.L. Jr. (2006) Characterization of the immune status of CD8+ T cells in oral lesions of human immunodeficiency virus-infected persons with oropharyngeal Candidiasis. Clin Vaccine Immunol 13, 678-683CrossRefGoogle ScholarPubMed
100Deitch, E.A. et al. (1995) Caco-2 and IEC-18 intestinal epithelial cells exert bactericidal activity through an oxidant-dependent pathway. Shock 4, 345-350CrossRefGoogle ScholarPubMed
101Jones-Carson, J. et al. (1995) Gamma delta T cell-induced nitric oxide production enhances resistance to mucosal candidiasis. Nat Med 1, 552-557CrossRefGoogle ScholarPubMed
102Dunsche, A. et al. (2001) Expression profile of human defensins and antimicrobial proteins in oral tissues. J Oral Pathol Med 30, 154-158CrossRefGoogle ScholarPubMed
103Dunsche, A. et al. (2002 ) The novel human beta-defensin-3 is widely expressed in oral tissues. Eur J Oral Sci 110, 121-124CrossRefGoogle ScholarPubMed
104Harder, J. et al. (2001) Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276, 5707-5713CrossRefGoogle ScholarPubMed
105Liu, A. et al. (2002) Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Investig Dermatol 118, 275-281CrossRefGoogle ScholarPubMed
106Mathews, M. et al. (1999) Production of beta- defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun Infect Immun 67, 2740-2745CrossRefGoogle ScholarPubMed
107Schroder, J.M. and Harder, J. (1999) Human beta-defensin-2. Int J Biochem Cell Biol 31, 645-651CrossRefGoogle ScholarPubMed
108Feng, Z. et al. (2005) Human beta-defensins: differential activity against candidal species and regulation by Candida albicans. J Dent Res 84, 445-450CrossRefGoogle ScholarPubMed
109Garcia, J.R. et al. (2001) Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res 306, 257-264CrossRefGoogle ScholarPubMed
110Nomanbhoy, F. et al. (2002) Vaginal and oral epithelial cell anti-Candida activity. Infect Immun 70, 7081-7088CrossRefGoogle ScholarPubMed
111Steele, C. (2001) Potential role for a carbohydrate moiety in anti-Candida activity of human oral epithelial cells. Infect Immun 69, 7091-7099CrossRefGoogle ScholarPubMed
112Yano, J. et al. (2005) Oral and vaginal epithelial cell anti-Candida activity is acid labile and does not require live epithelial cells. Oral Microbiol Immunol 20, 199-205CrossRefGoogle Scholar
113Sakai, A. et al. (2007) Potential role of high molecular weight hyaluronan in the anti-Candida activity of human oral epithelial cells. Med Mycol 45, 73-79CrossRefGoogle ScholarPubMed
114Cantorna, M.T. and Balish, E. (1991) Role of CD4+ lymphocytes in resistance to mucosal candidiasis. Infect Immun 59, 2447-2455CrossRefGoogle ScholarPubMed
115Farah, C.S. and Ashman, R.B. (2005) Active and passive immunization against oral Candida albicans infection in a murine model. Oral Microbiol Immunol 20, 376-381CrossRefGoogle ScholarPubMed
116De Luca, A. et al. (2007) Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J Immunol 179, 5999-6008CrossRefGoogle ScholarPubMed
117Montagnoli, C. et al. (2002) B7/CD28-dependent CD4 + CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J Immunol 169, 6298-6308CrossRefGoogle ScholarPubMed
118Sutmuller, R.P. et al. (2006) Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest 116, 485-494CrossRefGoogle ScholarPubMed
119Zelante, T. et al. (2007) IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol 37, 2695-2706CrossRefGoogle ScholarPubMed
120LeibundGut-Landmann, S. et al. (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8, 630-638CrossRefGoogle Scholar
121Veldhoen, M. et al. (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189CrossRefGoogle ScholarPubMed
122Mangan, P.R. et al. (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441, 231-234CrossRefGoogle Scholar
123Bettelli, E. et al. (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238CrossRefGoogle ScholarPubMed
124Ivanov, S. et al. (2007) Functional relevance of the IL-23-IL-17 axis in lungs in vivo. Am J Respir Cell Mol Biol 36, 442-451CrossRefGoogle ScholarPubMed
125Aggarwal, S. et al. (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278, 1910-1914CrossRefGoogle ScholarPubMed
126Langrish, C.L. et al. (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201, 233-240CrossRefGoogle ScholarPubMed
127Acosta-Rodriguez, E.V. et al. (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8, 639-646CrossRefGoogle ScholarPubMed
128Weaver, C.T. et al. (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25, 821-852CrossRefGoogle ScholarPubMed
129Huang, W. et al. (2004) Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis 190, 624-631CrossRefGoogle ScholarPubMed
130Rogers, T.R. (2006) Antifungal drug resistance: limited data, dramatic impact? Int J Antimicrob Agents 27 Suppl 1, 7-11CrossRefGoogle ScholarPubMed
131Schaller, M. et al. (2004) Polymorphonuclear leukocytes (PMNs) induce protective Th1-type cytokine epithelial responses in an in vitro model of oral candidosis. Microbiology 150, 2807-2813CrossRefGoogle Scholar
132Tardif, F. et al. (2004) Involvement of interleukin-18 in the inflammatory response against oropharyngeal candidiasis. Med Sci Monit 10, 239-249Google ScholarPubMed
133Ziege, S.U. et al. (2000) In vitro effects of interleukin-10, prednisolone, and GM-CSF on the non-specific immune function of human polymorphonuclear leucocytes and monocytes. Eur J Med Res 5, 369-374Google ScholarPubMed
134Richardson, M.D., Brownlie, C.E. and Shankland, G.S. (1992) Enhanced phagocytosis and intracellular killing of Candida albicans by GM-CSF-activated human neutrophils. J Med Vet Mycol 30, 433-441CrossRefGoogle ScholarPubMed
135Kurt-Jones, E.A. et al. (2002) Role of toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils. Blood 100, 1860-1868CrossRefGoogle ScholarPubMed
136Willment, J.A. et al. (2003) Dectin-1 expression and function are enhanced on alternatively activated and GM-CSF-treated macrophages and are negatively regulated by IL-10, dexamethasone, and lipopolysaccharide. J Immunol 171, 4569-4573CrossRefGoogle ScholarPubMed
137van Eijk, M. et al. (2005) Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity. Int Immunol 17, 1505-1512CrossRefGoogle ScholarPubMed
138Vazquez, J.A., Gupta, S. and Villanueva, A. (1998) Potential utility of recombinant human GM-CSF as adjunctive treatment of refractory oropharyngeal candidiasis in AIDS patients. Eur J Clin Microbiol Infect Dis 17, 781-783CrossRefGoogle ScholarPubMed
139Vazquez, J.A., Hidalgo, J.A. and De Bono, S. (2000) Use of sargramostim (rh-GM-CSF) as adjunctive treatment of fluconazole-refractory oropharyngeal candidiasis in patients with AIDS: a pilot study. HIV Clin Trials 1, 23-29CrossRefGoogle ScholarPubMed
140Clemons, K.V. and Stevens, D.A. (2000) Treatment of orogastrointestinal candidosis in SCID mice with fluconazole alone or in combination with recombinant granulocyte colony-stimulating factor or interferon-gamma. Med Mycol 38, 213-219CrossRefGoogle ScholarPubMed
141Gallin, J.I. et al. (1995) Interferon-gamma in the management of infectious diseases. Ann Intern Med 123, 216-224CrossRefGoogle ScholarPubMed
142Murray, H.W. (1994) Interferon-gamma and host antimicrobial defense: current and future clinical applications. Am J Med 97, 459-467CrossRefGoogle ScholarPubMed
143Torrico, F. et al. (1991) Endogenous IFN-gamma is required for resistance to acute Trypanosoma cruzi infection in mice. J Immunol 146, 3626-3632CrossRefGoogle ScholarPubMed
144Bodasing, N. et al. (2002) Gamma-interferon treatment for resistant oropharyngeal candidiasis in an HIV-positive patient. J Antimicrob Chemother 50, 765-766CrossRefGoogle Scholar
145Ohta, H. et al. (2007) Regulation of Candida albicans morphogenesis by tumor necrosis factor-alpha and potential for treatment of oral candidiasis. In Vivo 21, 25-32Google ScholarPubMed
146Gamble, J.R. et al. (1985) Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A 82, 8667-8671CrossRefGoogle ScholarPubMed
147Rice, P.J. et al. (2005) Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. J Pharmacol Exp Ther 314, 1079-1086CrossRefGoogle ScholarPubMed
148Verstak, B., Hertzog, P. and Mansell, A. (2007) Toll-like receptor signalling and the clinical benefits that lie within. Inflamm Res 56, 1-10CrossRefGoogle Scholar
149Garay, R.P. et al. (2007) Cancer relapse under chemotherapy: why TLR2/4 receptor agonists can help. Eur J Pharmacol 563, 1-17CrossRefGoogle ScholarPubMed
150Re, F. and Strominger, J.L. (2004) IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. J Immunol 173, 7548-7555CrossRefGoogle ScholarPubMed
151Namba, K. et al. (1997) Romurtide, a synthetic muramyl dipeptide derivative, promotes megakaryocytopoiesis through stimulation of cytokine production in nonhuman primates with myelosuppression. Vaccine 15, 405-413CrossRefGoogle ScholarPubMed
152Onier, N. et al. (1999) Expression of inducible nitric oxide synthase in tumors in relation with their regression induced by lipid A in rats. Int J Cancer 81, 755-7603.0.CO;2-3>CrossRefGoogle ScholarPubMed
153Spellberg, B.J. et al. (2005) The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect Immun 73, 6191-6193CrossRefGoogle ScholarPubMed
154Spellberg, B.J. et al. (2006) Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis 194, 256-260CrossRefGoogle ScholarPubMed
155Ibrahim, A.S. et al. (2006) The anti-Candida vaccine based on the recombinant N-terminal domain of Als1p is broadly active against disseminated candidiasis. Infect Immun 74, 3039-3041CrossRefGoogle ScholarPubMed
156Ibrahim, A.S. et al. (2005) Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect Immun 73, 999-1005CrossRefGoogle Scholar

Further reading, resources and contacts

Gantner, B. N., Simmons, R. M. and Underhill, D. M. (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24, 1277-1286CrossRefGoogle Scholar
Kennedy, A. D., et al. (2007) Dectin-1 promotes fungicidal activity of human neutrophils. Eur J Immunol 37, 467-478CrossRefGoogle ScholarPubMed
Acosta-Rodriguez, E. V., et al. (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8, 639-646CrossRefGoogle ScholarPubMed
Zelante, T., et al. (2007) IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol 37, 2695-2706CrossRefGoogle ScholarPubMed
Gantner, B. N., Simmons, R. M. and Underhill, D. M. (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24, 1277-1286CrossRefGoogle Scholar
Kennedy, A. D., et al. (2007) Dectin-1 promotes fungicidal activity of human neutrophils. Eur J Immunol 37, 467-478CrossRefGoogle ScholarPubMed
Acosta-Rodriguez, E. V., et al. (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8, 639-646CrossRefGoogle ScholarPubMed
Zelante, T., et al. (2007) IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol 37, 2695-2706CrossRefGoogle ScholarPubMed