Introduction: 
Farnesol, the first quorum sensing molecule described in eukaryotes, is produced by Candida albicans and controls filamentation in these fungi. The mechanism of how farnesol blocks the C. albicans yeast to hyphae transition is well known; however, the impact of farnesol on host cells is poorly understood, especially on dendritic cells (DCs) which are key regulators of immunity against C. albicans. The aim of this study is to evaluate the effect of farnesol on dendritic cell differentiation and maturation by analyzing the phenotype, transcriptional profile and functionality.

Methods: 
Monocytes were differentiated into DCs in presence or absence of farnesol, PPARγ and RARα agonist and antagonist. Transcriptional analysis of DCs in response to farnesol was performed by a microarray assay. DCs immunophenotype was addressed by flow cytometry. iNKT proliferation was adressed by a DCs-T-cells co-culture and PPARγ and RARα activation was measured by qRT-PCR. 

Results: 
Farnesol treatment impaired surface expression of key markers for maturation and antigen presentation (CD80 and CD86). Furthermore, farnesol modulates the displacement of CD1 molecules. While CD1a showed reduced expression; CD1d, a molecule involved in invariant Natural Killer T (iNKT) cell activation, was increased on DCs generated in the presence of farnesol. Nevertheless, these cells have reduced capacity to prime iNKT. The microarray analysis showed a high number of differentially regulated genes included in nuclear receptors pathway. Interestingly, we found an elevated activation of PPARγ and RARα, and the use of antagonists for these nuclear receptors blocked the effects of farnesol on the expression of CD1 and costimulatory molecules.

Conclusion: 
Our results suggest that farnesol regulates DCs phenotype and induce transcriptional rewiring in these cells. This quorum sensing molecule affects costimulatory and CD1 molecules expression by PPARγ and RARα activation; nevertheless, these cells have a decreased capacity to activate iNKT cells. Further experiments will be performed in order to elucidate alternate pathways involved in farnesol-treated DCs.

Candida albicans quorum sensing molecule Farnesol modulates human dendritic cells function by nuclear receptors activation