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Infection and Immunity, August 2007, p. 4006-4011, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00397-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model

School of Biological Sciences,¹ Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska,² Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska,³ Department of Oral Biology, University of Nebraska Medical Center, Lincoln, Nebraska⁴

Received 15 March 2007/ Returned for modification 25 April 2007/ Accepted 7 May 2007

Candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the most common human fungal pathogen. Th1 cytokines such as interleukin-2 (IL-2), gamma interferon (IFN-), and tumor necrosis factor alpha (TNF-), which are induced by macrophage IL-12, are critical to resistance against systemic candidiasis, while Th2 cytokines such as IL-4 and IL-5 are less critical. Farnesol is a quorum-sensing molecule produced by C. albicans that controls the formation of mycelia but is also a virulence factor. To determine whether farnesol enhances the virulence of C. albicans by modulating the production of Th1 and Th2 cytokines, mice were pretreated with farnesol prior to intravenous infection with a sublethal dose of farnesol-producing C. albicans. Production of IL-2, IL-4, IL-5, TNF-, IFN-, and IL-12 was evaluated by bead-array flow cytometry and enzyme-linked immunosorbent assay. Mice exhibited an elevation in serum TNF- levels at 48 h and an elevation in IFN- and IL-12 levels at 6 to 12 h after infection with C. albicans. Pretreatment with farnesol significantly reduced the elevation of both IFN- and IL-12 but not TNF-. In contrast, mice pretreated with farnesol exhibited an unexpected elevation in IL-5 levels. To determine whether farnesol has a direct effect on macrophage production of IL-12, peritoneal macrophages were pretreated with farnesol prior to stimulation with IFN- plus lipopolysaccharide (LPS). Farnesol inhibited production of both IL-12 p40 and p70 from IFN-/LPS-stimulated macrophages. Therefore, the role of farnesol in systemic candidiasis is likely due to its ability to inhibit the critical Th1 cytokines IFN- and IL-12 and perhaps to enhance a Th2 cytokine, IL-5.

Published ahead of print on 21 May 2007.

Editor: A. Casadevall

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