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FEMS Immunol Med Microbiol. 2010 Oct;60(1):63-73. doi: 10.1111/j.1574-695X.2010.00717.x.

Candida albicans cell wall components and farnesol stimulate the expression of both inflammatory and regulatory cytokines in the murine RAW264.7 macrophage cell line.

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1
School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.

Abstract

Candida albicans causes candidiasis, secretes farnesol, and switches from yeast to hyphae to escape from macrophages after phagocytosis. However, before escape, macrophages may respond to C. albicans' pathogen-associated molecular patterns (PAMPs) through toll-like receptor 2 (TLR2) and dectin-1 receptors by expressing cytokines involved in adaptive immunity, inflammation, and immune regulation. Therefore, macrophages and the RAW264.7 macrophage line were challenged with C. albicans preparations of live wild-type cells, heat-killed cells, a live mutant defective in hyphae formation, a live mutant producing less farnesol, or an isolate producing farnesoic acid instead of farnesol. Interleukin-6 (IL-6), and IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) expression were evaluated by ELISA and/or qRT-PCR within 6 h after challenge. All viable strains producing farnesol, regardless of hyphae phenotype, induced IL-6, IL-1β, IL-10, and TNF-α. To determine which components of C. albicans induced IL-6, RAW264.7 cells were incubated with farnesol, farnesoic acid, with or without zymosan, a yeast cell wall preparation that contains PAMPs recognized by TLR2 and dectin-1. The highest expression of IL-6, TLR2, and dectin-1 occurred when RAW264.7 cells were stimulated with zymosan and farnesol together. Our results suggest that the rapid expression of cytokines from macrophages challenged with C. albicans is due to cell-wall PAMPs combined with farnesol.

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