Impact of the fungal quorum sensing molecule farnesol on human innate immune cells
Quorum sensing (QS) is a cell density-dependent mechanism that affects microbial metabolism and gene expression. In fungi, the QS phenomenon has first been described for the opportunistic pathogen C. albicans, which produces farnesol as a QS molecule to regulate virulence determinants. Aside from controlling morphogenesis, the impact of farnesol throughout the infection process has been only partially elucidated. The aim of this study was to unravel the impact of farnesol on innate immune cells important for fungal clearance and protective immune response. Therefore, neutrophils, monocytes and dendritic cells (DC) were investigated concerning phenotype and effector mechanisms. Farnesol activated neutrophils and monocytes, reflected in an enhanced expression of activation markers on the surface of both immune cells and in an increased release of proteolytic enzymes by neutrophils and pro-inflammatory cytokines by monocytes. This low-grade activation was not sufficient to influence fungicidal activity of neutrophils and monocytes towards C. albicans. The greatest impact of farnesol was found on the differentiation process of human monocytes into mature DC. Substantial changes were observed to the differentiation phenotype characterized by reduced expression of markers important for maturation and antigen presentation. Furthermore, farnesol influenced the release of a variety of inflammatory cytokines and chemokines, wherein the secretion of Th1-inducing cytokines such as IL 12 were markedly reduced. Limitations in mobility and a reduced T cell stimulatory capacity of DC generated in the presence of farnesol were ascertained and suggest an immunomodulatory function of farnesol. Altogether, this study promotes the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and dampening the Th1 response which is essential for fungal clearance.