Abstract
BACKGROUND: Vulvovaginal candidiasis (VVC), mainly caused by Candida albicans, affects approximately 75% of women at least once during their lifetime. VVC is characterized by fungal colonization, which leads to inappropriate local hyperinflammation and symptoms. Although the trigger of C. albicans pathogenicity is often unknown, antibiotic use and vaginal dysbiosis are associated with increased susceptibility to VVC. A healthy vaginal microbiota is normally dominated by Lactobacillus species, which are believed to keep C. albicans infections at bay. Probiotic lactobacilli are, therefore, explored to treat symptomatic VVC episodes. However, the influence of probiotic lactobacilli on immune responses in the context of VVC remains underexplored. METHODS: We investigated how probiotic lactobacilli influence vaginal epithelial and downstream inflammatory responses during C. albicans infection, using in vitro vaginal epithelial infection models and stimulating primary human immune cells with supernatants from these vaginal epithelial cells. RESULTS: Our study shows that although most of the tested probiotic lactobacilli reduced C. albicans-induced vaginal epithelial cell damage, some species, particularly Limosilactobacillus fermentum and Lacticaseibacillus paracasei, elicited proinflammatory responses even in the absence of C. albicans. Probiotic lactobacilli also differentially modulated the C. albicans killing efficiency and production of reactive oxygen species by neutrophils. CONCLUSIONS: Overall, vaginal epithelial and downstream immune responses during co-cultivation with C. albicans and probiotic lactobacilli were mostly driven by specific bacterial species and their interactions with the vaginal epithelium. Therefore, the induction of "controlled" inflammation by probiotic lactobacilli may be beneficial to improve neutrophil function; however, whether this alleviates immunopathology warrants further investigation.