Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of
farnesol on innate immune cells known to be important for fungal clearance and protective immunity.
Farnesol enhanced the expression of activation markers on monocytes (CD86 and
HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory
cytokines (
tumor necrosis factor alpha [TNF-α] and
macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by
farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of
farnesol. Furthermore,
farnesol modulated migrational behavior and
cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of
interleukin 12 (IL-12) induction in iDC generated in the presence of
farnesol. Transcriptome analyses revealed a
farnesol-induced shift in effector molecule expression and a down-regulation of the
granulocyte-macrophage colony-stimulating factor (
GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of
farnesol to act as a
virulence factor of C. albicans by influencing innate immune cells to promote
inflammation and mitigating the Th1 response, which is essential for fungal clearance.
IMPORTANCE:
Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of
farnesol on human innate immune cells known to be important for fungal clearance and protective immunity. We show that
farnesol is able to enhance
inflammation by inducing activation of neutrophils and monocytes. At the same time,
farnesol impairs differentiation of monocytes into immature dendritic cells (iDC) by modulating surface phenotype,
cytokine release and migrational behavior. Consequently, iDC generated in the presence of
farnesol are unable to induce proper T cell responses and fail to secrete Th1 promoting
interleukin 12 (IL-12). As
farnesol induced down-regulation of the
granulocyte-macrophage colony-stimulating factor (
GM-CSF) receptor, desensitization to
GM-CSF could potentially explain transcriptional reprofiling of iDC effector molecules. Taken together, our data show that
farnesol can also mediate Candida-host communication and is able to act as a
virulence factor.