Mediation of Candida species growth and virulence by the proinflammatory cytokine IL-6

Abstract Interleukin-6 (IL-6) is a cytokine with pleiotropic effects that might also influence the virulence traits of some microorganisms, but its direct influence over Candida spp. is currently unknown. The objective of the study is to determine the influence of IL-6 (250 pg/ml) on the growth rate and biofilm formation of C. albicans, C. parapsilosis, C. krusei, C. auris, and C. guilliermondii, as well as to analyze the influence of this citokine on the expression of three virulence genes (ALS3, HSP70, SAP2), respectively on the germ tube formation ability of C. albicans. The influence of IL-6 on growth rate was assessed by incubating the fungal cells in presence of IL-6 for 48 hours and assessing the optical density of the samples at five timepoints. The biofilm production in presence of IL-6 was studied in microtiter plates, using crystal-violet assay, the intensity of biofilms being evaluated by spectrophotometry. The expression of ALS3, HSP70, and SAP2 in C. albicans was studied by RT-PCR, reported to ACT1 housekeeping gene. The germ-tube test was performed to assess the influence of IL-6 on the filamentation rate of C. albicans. All test results were normalized against control, without added IL-6. The results showed that IL-6 influences the growth rate of C. albicans, C. parapsilosis, C. krusei, C. auris, and C. guilliermondii in a time-dependent way. Also, IL-6 inhibited the formation of biofilms for C. albicans and C. guilliermondii. In C. albicans cells, IL-6 induced upregulation of ALS3 and HSP70, while it down-regulated the SAP2 gene. IL-6 did not influence the germ-tube formation in C. albicans. In conclusion, IL-6 might exert, in vitro, direct effects on the virulence traits of Candida spp., and its influence is dependent on the exposure time. Non-albicans Candida species presented particular responses to IL-6.