THE PROTECTIVE ROLE OF TYPE-I INTERFERONS AXIS ACTIVATION IN THE VULVOVAGINAL CANDIDIASIS MODEL

Background and Aims: Previously, in an in-vitro model of epidermoid carcinoma A431 cells line, we observed that the commensal Candida albicans Ca4314 strain up-regulates the type I interferons pathway in comparison to the vulvovaginal candidiasis-associated strain Ca1887. Here, we aim to test the protective role of type I interferons pathway activation in reducing fungal proliferation and inflammasome involvement. Methods: We co-cultured A431 cells with Ca4314 and Ca1887 strains for 1.5h, then we measured the expression of interferon regulatory factor 3 (IRF3). Further, we blocked the type I interferons pathway by anti-IFNAR Ab. Fungal shedding was evaluated on exfoliated and loosely-adherent cells after 24h of co-incubation. Separately, the supernatants were analyzed for Lactate Dehydrogenase assay (LDH) release and inflammasome markers production. Results: We observed significantly higher intracellular expression of IRF3 in A431 cells co-incubated with Ca4314 compared to Ca1887. The analysis of colony forming units showed greater shedding of Ca1887 compared to Ca4314. The ?-IFNAR Ab increased shedding of Ca4314 but this effect was not observed with Ca1887. LDH analysis showed a high level of cell damage induced by Ca1887, in contrast to Ca4314. Finally, we found increased inflammasome markers production in supernatant isolated from Ca1887 compared to those from Ca4314. Conclusions: Our findings suggest a model in which type I interferons axis activation protects the epithelial cells from damage induced by Candida, limiting fungal shedding and inflammasome involvement. Taken together, our data suggest that modulation of the type I interferons pathway may regulate the pathogenic impact of Candida during vaginal infection.