Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model

Dhammika H M L P Navarathna, Kenneth Nickerson, Gerald E. Duhamel, Thomas R. Jerrels, Thomas M Petro

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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-γ), and tumor necrosis factor alpha (TNF-α), 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-α, IFN-γ, and IL-12 was evaluated by bead-array flow cytometry and enzyme-linked immunosorbent assay. Mice exhibited an elevation in serum TNF-α levels at 48 h and an elevation in IFN-γ and IL-12 levels at 6 to 12 h after infection with C. albicans. Pretreatment with farnesol significantly reduced the elevation of both IFN-γ and IL-12 but not TNF-α. 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-γ plus lipopolysaccharide (LPS). Farnesol inhibited production of both IL-12 p40 and p70 from IFN-γ/LPS-stimulated macrophages. Therefore, the role of farnesol in systemic candidiasis is likely due to its ability to inhibit the critical Th1 cytokines IFN-γ and IL-12 and perhaps to enhance a Th2 cytokine, IL-5.

Original languageEnglish (US)
Pages (from-to)4006-4011
Number of pages6
JournalInfection and immunity
Volume75
Issue number8
DOIs
StatePublished - Aug 1 2007

Fingerprint

Farnesol
Candidiasis
Interleukin-12
Cytokines
Candida albicans
Interleukin-5
Macrophages
Interleukin-4
Interleukin-2
Lipopolysaccharides
Quorum Sensing
Mycelium
Peritoneal Macrophages
Virulence Factors
Infection
Interferon-gamma
Virulence
Flow Cytometry
Fungi
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model. / Navarathna, Dhammika H M L P; Nickerson, Kenneth; Duhamel, Gerald E.; Jerrels, Thomas R.; Petro, Thomas M.

In: Infection and immunity, Vol. 75, No. 8, 01.08.2007, p. 4006-4011.

Research output: Contribution to journalArticle

Navarathna, Dhammika H M L P ; Nickerson, Kenneth ; Duhamel, Gerald E. ; Jerrels, Thomas R. ; Petro, Thomas M. / Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model. In: Infection and immunity. 2007 ; Vol. 75, No. 8. pp. 4006-4011.
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