Differential Virulence of Vaginal Candida albicans Isolates Correlates with Host Inflammatory Responses in VVC/RVVC

Candida albicans (C. albicans) is a commensal of the vaginal mucosa and the main etiological agent of acute and recurrent vulvovaginal candidiasis (VVC/RVVC). Disease severity is thought to depend on a dysregulated host inflammatory response to Candida, not necessarily associated with increased fungal burden and/or morphogenesis. The role of strain-specific differences leading to epithelial immune response or tolerance remains undefined. In this study, we compared the virulence profile of vaginal C. albicans isolates from women with acute VVC/RVVC (VVC/RVVC), asymptomatic colonizer (Colonizing), and VVC/RVVC associated with microbial co-infections (Co-infections). Isolates were evaluated for growth and biofilm formation under standard culture conditions and tested in an in vitro vaginal epithelial cell (VEC) infection model to assess fungal shedding, epithelial damage, and cytokine production. Corresponding vaginal samples were analyzed for C. albicans morphology, polymorphonuclear neutrophil presence, microbiota composition, cytokines levels, and anti-C. albicans IgA production. No significant differences in growth or biofilm formation were observed among isolates under culture conditions. However, VEC infection revealed strain-dependent differences: acute VVC/RVVC and Co-infections isolates induced greater fungal shedding, while VVC/RVVC isolates caused increased epithelial damage and showed a trend toward higher cytokine production. Vaginal samples from symptomatic groups displayed increased neutrophils, hyphal morphology, elevated IL-1α, IL-1β, and anti-Candida IgA, but not IL-1Ra, without differences in lactobacilli abundance or Community-State-Type (CST) distribution. These findings suggest that C. albicans pathogenicity in VVC depends on strain-specific interactions with VEC driving differential host responses.