title: Candida albicans cell wall components and farnesol stimulate the expression of both inflammatory and regulatory cytokines in the murine RAW264.7 macrophage cell line.
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.
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Ghosh
authors.forename: Nina
authors.initials: N
authors.lastname: Howe
authors.forename: Katie
authors.initials: K
authors.lastname: Volk
authors.forename: Swetha
authors.initials: S
authors.lastname: Tati
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Nickerson
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Petro
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005204:Farnesol / Q000276:immunology* / Q000302:isolation & purification; D015870:Gene Expression; D020869:Gene Expression Profiling; D037181:Lectins, C-Type; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D005204:Farnesol; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D000099181:Dectin-1; C493486:Tlr2 protein, mouse