Farnesol, a Quorum-Sensing Molecule of Candida Albicans Triggers the Release of Neutrophil Extracellular Traps

The efficient growth of pathogenic bacteria and fungi in the host organism is possible due to the formation of microbial biofilms that cover the host tissues. Biofilms provide optimal local environmental conditions for fungal cell growth and increased their protection against the immune system. A common biofilm-forming fungus-Candida albicans-uses the quorum sensing (QS) mechanism in the cell-to-cell communication, which determines the biofilm development and, in consequence, host colonization. In the presented work, we focused on the ability of neutrophils-the main cells of the host's immune system to recognize quorum sensing molecules (QSMs) produced by C. albicans, especially farnesol (FOH), farnesoic acid (FA), and tyrosol (TR), with emphasis on the neutrophil extracellular traps (NETs) formation in a process called netosis. Our results showed for the first time that only farnesol but not farnesolic acid or tyrosol is capable of activating the NET production. By using selective inhibitors of the NET signaling pathway and analyzing the activity of selected enzymes such as Protein Kinase C (PKC), ERK1/2, and NADPH oxidase, we showed that the Mac-1 and TLR2 receptors are responsible for FOH recognizing and activating the reactive oxygen species (ROS)-dependent netosis pathway.