Suppression of anti‐Candida activity of macrophages by a quorum‐sensing molecule, farnesol, through induction of oxidative stress

Abstract

Farnesol is well known as a quorum-sensing molecule of Candida albicans. To assess the pathological function of farnesol, its effects on macrophage viability and functions including growth inhibitory activities against C. albicans were examined in vitro. Murine macrophages, when cultured in the presence of 56-112 μM of farnesol for 1-2 hr, decreased their activity inhibiting the mycelial growth of C. albicans and lost their viability. This suppression of macrophage function by farnesol was neutralized by the coexistence of the anti-oxidants probucol and trolox. Macrophages cultured in the presence of farnesol for 2 hr displayed morphological change of nuclei and DNA fragmentation, which suggested apoptosis of the cells. Intracellular production of ROS in the farnesol-treated macrophages was shown by fluorescence of DCFH-DA and increase of peroxidized materials. These effects of farnesol were blocked by probucol or trolox. These results indicate that farnesol lowered viability of the murine macrophages and suppressed their anti-Candida activity, perhaps through induction of ROS.

Candida Survival Strategies

“…Farnesol modulates the immune response toward a nonprotective Th2 response rather than a protective Th1 response, inducing IL-5 rather than Interferon gamma (IFNg) and IL-12 . It furthermore inhibits IL-6 cytokine production in murine macrophages, a key cytokine in mucosal and systemic C. albicans infections, and induces apoptosis of macrophages (Abe et al, 2009;Conti et al, 2009;Ghosh et al, 2010). In contrast to its function as a virulence factor in a systemic model, exogenously added farnesol exerted a protective effect on cells in a reconstituted human epithelial (RHE) model and in a mouse model of oral candidiasis (Hisajima et al, 2008;Saidi, Luitaud, & Rouabhia, 2006).…”

Quorum sensing and fungal-bacterial interactions inCandida albicans: a communicative network regulating microbial coexistence and virulence

“…However, although farnesol does not affect C. albicans growth, a strong antifungal and antibacterial activity has been reported against several other organisms including Aspergillus nidulans and Saccharomyces cerevisiae (Tseng & Fink, 2008) conferring a selective advantage in the environment. Farnesol has also been shown to decrease the viability of murine macrophages (Abe et al, 2009). Farnesol has also been shown to decrease the viability of murine macrophages (Abe et al, 2009).…”

Quorum sensing in fungi – a review

“…Farnesol also inhibited murine macrophage antifungal activity against C. albicans by inducing oxidative stress and apoptosis of macrophages [33]. Finally, farnesol induced apoptosis and necrosis of human spermatozoa suggesting a possible link between microbes and host infertility [35].…”