Differential Virulence of Vaginal Candida albicans IsolatesC orrelates 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.