This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van der Graaf, C. A. A. Articles by Kullberg, B. J. Search for Related Content PubMed PubMed Citation Articles by van der Graaf, C. A. A. Articles by Kullberg, B. J.

 Previous Article  |  Next Article 

Infection and Immunity, November 2005, p. 7458-7464, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7458-7464.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Differential Cytokine Production and Toll-Like Receptor Signaling Pathways by Candida albicans Blastoconidia and Hyphae

Department of Medicine, Radboud University Nijmegen Medical Center,¹ Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands²

Received 18 May 2005/ Returned for modification 28 June 2005/ Accepted 16 August 2005

Toll-like receptors (TLR) are crucial for an efficient antifungal defense. We investigated the differential recognition of blastoconidia and hyphae of Candida albicans by TLRs. In contrast to Candida blastoconidia, which stimulated large amounts of gamma interferon (IFN-), the tissue-invasive Candida hyphae did not stimulate any IFN- by human peripheral blood mononuclear cells (PBMC) or murine splenic lymphocytes. After stimulation with blastoconidia, the production of IFN- was TLR4 dependent, as shown by the significantly decreased IFN- production in anti-TLR4-treated PBMC and in splenic lymphocytes from TLR4-defective ScCr mice. In addition, peritoneal macrophages from ScCr mice produced less tumor necrosis factor (TNF-) than macrophages of control mice did when stimulated with Candida blastoconidia, but not with hyphae, indicating that TLR4-mediated signals are lost during hyphal germination. In contrast, macrophages from TLR2 knockout mice had a decreased production of TNF- in response to both Candida blastoconidia and hyphae. Candida hyphae stimulated production of interleukin-10 through TLR2-dependent mechanisms. In conclusion, TLR4 mediates proinflammatory cytokine induction after Candida stimulation, whereas Candida recognition by TLR2 leads mainly to anti-inflammatory cytokine release. TLR4-mediated proinflammatory signals are lost during germination of Candida blastoconidia into hyphae. Phenotypic switching during germination may be an important escape mechanism of C. albicans, resulting in counteracting host defense.

Editor: T. R. Kozel

This article has been cited by other articles:

• Grubb, S. E. W., Murdoch, C., Sudbery, P. E., Saville, S. P., Lopez-Ribot, J. L., Thornhill, M. H. (2008). Candida albicans-Endothelial Cell Interactions: a Key Step in the Pathogenesis of Systemic Candidiasis. Infect. Immun. 76: 4370-4377 [Full Text]  
• Tarabishy, A. B., Aldabagh, B., Sun, Y., Imamura, Y., Mukherjee, P. K., Lass, J. H., Ghannoum, M. A., Pearlman, E. (2008). MyD88 Regulation of Fusarium Keratitis Is Dependent on TLR4 and IL-1R1 but Not TLR2. J. Immunol. 181: 593-600 [Abstract] [Full Text]  
• Weck, M. M., Appel, S., Werth, D., Sinzger, C., Bringmann, A., Grunebach, F., Brossart, P. (2008). hDectin-1 is involved in uptake and cross-presentation of cellular antigens. Blood 111: 4264-4272 [Abstract] [Full Text]  
• Westwater, C., Balish, E., Warner, T. F., Nicholas, P. J., Paulling, E. E., Schofield, D. A. (2007). Susceptibility of gnotobiotic transgenic mice (Tg{epsilon}26) with combined deficiencies in natural killer cells and T cells to wild-type and hyphal signalling-defective mutants of Candida albicans. J Med Microbiol 56: 1138-1144 [Abstract] [Full Text]  
• Chandra, J., McCormick, T. S., Imamura, Y., Mukherjee, P. K., Ghannoum, M. A. (2007). Interaction of Candida albicans with Adherent Human Peripheral Blood Mononuclear Cells Increases C. albicans Biofilm Formation and Results in Differential Expression of Pro- and Anti-Inflammatory Cytokines. Infect. Immun. 75: 2612-2620 [Abstract] [Full Text]  
• Fradin, C., Mavor, A. L., Weindl, G., Schaller, M., Hanke, K., Kaufmann, S. H. E., Mollenkopf, H., Hube, B. (2007). The Early Transcriptional Response of Human Granulocytes to Infection with Candida albicans Is Not Essential for Killing but Reflects Cellular Communications. Infect. Immun. 75: 1493-1501 [Abstract] [Full Text]  
• Levy, O., Coughlin, M., Cronstein, B. N., Roy, R. M., Desai, A., Wessels, M. R. (2006). The Adenosine System Selectively Inhibits TLR-Mediated TNF-{alpha} Production in the Human Newborn. J. Immunol. 177: 1956-1966 [Abstract] [Full Text]  
• Kosonen, J., Rantala, A., Little, C. H., Lintu, P., Harjamaki, P.-R., Georgiou, G. M., Cone, R. E., Savolainen, J. (2006). Increased Levels of Candida albicans Mannan-Specific T-Cell-Derived Antigen Binding Molecules in Patients with Invasive Candidiasis. CVI 13: 467-474 [Abstract] [Full Text]