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, its direct influence over Candida spp. being currently unknown. The objective of the study is to determine the influence of IL-6 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 IL-6 on the expression of three virulence genes (ALS3, HSP70, and SAP2) and the germ tube formation ability of C. albicans. The influence of IL-6 on fungal growth rate was assessed by incubating the fungal cells in the presence of IL-6 (62.5-500 pg/ml) for 48 hours and reading the optical density of the samples at five timepoints. The biofilm production was studied by incubating the fungal cells in the presence of IL-6 (250 pg/ml) in sterile microtiter plates for 24 hours. The formation of biofilms was appreciated by spectrophotometry. The expression of ALS3, HSP70, and SAP2 in C. albicans was studied by qRT-PCR. The germ-tube test was performed to assess the influence of IL-6 on the filamentation rate of C. albicans. 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 the upregulation of ALS3 and HSP70, while it down-regulated the SAP2 gene. In conclusion, IL-6 might extent direct effects in vitro on the virulence traits of Candida spp its influence being dependent on the exposure time and IL-6 concentration. Non-albicans species presented particular responses to IL-6.

Keywords: growth rate, biofilms, ALS3, HSP70, SAP2, Candida