Vaginal transcriptional signatures of the neutrophil-driven immune response correlate with clinical severity during recurrent vulvovaginal candidiasis

Problem: Recurrent vulvovaginal candidiasis (RVVC) affects 5-10% of all women, negatively impacting their reproductive health and quality of life. Herein, we investigated the molecular effects of RVVC on the vaginal mucosa of otherwise healthy women. Methods: Gene expression analysis was performed on vaginal tissue biopsies from women with RVVC, including those with a current episode of vulvovaginal candidiasis (RVVC, n=19) and women between infections (CNR, n=8); women asymptomatically colonized with Candida albicans (AS, n=7); and healthy controls (n=18). Gene expression profiles were compared between groups and correlated with clinical data retrieved from questionnaires and gynecologic examinations. Results: Of 20,171 genes identified in vaginal biopsies, 6,506 were differentially expressed in the RVVC group, compared to healthy controls. Gene expression pathway analysis revealed an association between RVVC and pathways of inflammatory responses, especially genes involved in neutrophil recruitment and activation. Expression of genes involved in inflammation and neutrophil recruitment increased with increasing clinical severity of vulvovaginal candidiasis, whereas expression of some genes involved in epithelial integrity decreased with increasing clinical severity of infection. Gene expression profiles of both the CNR and AS groups were comparable to those of healthy controls. Conclusions: The clinical severity of RVVC during active infection correlates with increased expression of genes involved in molecular inflammation and neutrophil activation in the vaginal mucosa. The lack of differences between healthy controls and women with RVVC who were between acute infections indicates that the molecular effects observed in the RVVC group are only present during active infection.