Interaction of Innate Immunity and Candida albicans Virulence Factors in the Regulation of the NLRP3 Inflammasome in Recurrent Vulvovaginal Candidiasis

Abstract Objective: Recurrent vulvovaginal candidiasis (RVVC) is currently considered an immunopathological process. Fungal virulence factors and host immune responses, such as NLRP3 inflammasome activation, are thought to play an important role in the development of hyperinflammation. The aim of this study was to investigate the expression patterns of genes encoding key molecules involved in the immunoregulation of the inflammatory response, C. albicans virulence factors, as well as cytokine levels in the vaginal fluid of patients with RVVC. Materials and methods: Gene expression encoding NLRP3, caspase-1 (CASP1), NLRC4, cytokines IL-1β, IL-18, IL-1Ra, and C. albicans virulence factors was determined in the cellular fraction of vaginal washes by quantitative polymerase chain reaction. The levels of IL-1β, IL-18, IL-22, and IL-1Ra were measured by enzyme-linked immunosorbent assay. Statistical analysis was performed using the Python programming language (pandas, numpy, scipy, statsmodels, and matplotlib libraries). Results: Increased NLRP3 inflammasome activity at the local level in RVVC patients was confirmed by enhanced expression of NLRP3, CASP1, and IL1B genes, as well as elevated IL-1β levels compared to the control group. In all RVVC patients, unlike healthy women, expression of the SAP2 gene, associated with the yeast form of C. albicans, as well as SAP5, SAP6, ECE1, and HWP1 genes associated with the yeast-to-hypha transition, was detected. The important role of candidalysin in NLRP3 inflammasome activation was confirmed by a strong correlation between CASP1 and ECE1 expression. A distinctive feature of women with candidal infection was a significant decrease in vaginal IL-18 and IL-1Ra levels, as well as a tendency toward reduced IL-22 concentrations. A negative correlation was found between IL-18 and IL-22 levels and the number of vulvovaginal candidiasis recurrences per year. Conclusion: In RVVC, the IL-18/IL-22/IL-1Ra axis at the local level counteracts C. albicans virulence factors in NLRP3 inflammasome activation and, consequently, prevents the transition of the inflammatory response to a chronic stage and the progression of fungal infection.