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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

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