Candida auris persists in the vaginal microaerobic niche in the absence of interleukin-17A.

Candida auris is an emerging fungus notable for its high drug resistance and persistent colonization of human hosts and environmental surfaces. However, its role in vulvovaginal candidiasis (VVC), a common form of superficial candidiasis, remains poorly understood. In this study, we investigated the colonization capacity of C. auris and vaginal defense mechanisms in a VVC model. Using an estrogenized VVC mouse model, we evaluated fungal burden, inflammatory cell counts, and S100A8 concentrations in vaginal lavages of wild-type (WT) and IL-17A knockout (Il17a^-/-) C57BL/6J mice following C. auris inoculation. Histopathological examination and flow cytometry analysis of vaginal immune cells were also conducted. Additionally, an in vitro adhesion assay was performed using VK2/E6E7 vaginal epithelial cells under aerobic and microaerobic conditions mimicking the vaginal environment. Persistent colonization by C. auris, particularly clades I, III, and IV, with minimal infiltration of inflammatory cells, was confirmed in Il17a^-/- mice. These findings were also supported by histopathological analysis. S100A8 concentration analysis revealed significant differences between WT and Il17a^-/- mice, with lower levels detected in the Il17a^-/- group. Furthermore, S100A8 levels showed positive correlations with inflammatory cell count and negative correlations with vaginal fungal burden. Flow cytometry analysis demonstrated a reduced number of vaginal neutrophils in Il17a^-/- mice. Additionally, in vitro adhesion assay revealed increased C. auris adherence to vaginal epithelial cells under microaerobic conditions. C. auris exhibits a strong affinity for the vaginal epithelium, and IL-17A appears to play a protective role in C. auris-associated VVC.

Importance: Candida auris is an emerging fungal species, and several reports have recently identified C. auris in patients with vulvovaginal candidiasis (VVC), although few studies have investigated the relationship between C. auris and VVC or the associated host factors. Our study, using the VVC mouse model, confirmed persistent vaginal colonization by C. auris, especially clades I, III, and IV, along with reduced neutrophil infiltration and lower S100A8 secretion under interleukin-17A-deficient conditions. In addition, in vitro assays demonstrated enhanced C. auris adhesion to vaginal epithelial cells, especially microaerobic conditions imitating human vaginal microenvironments. Our findings suggest that C. auris exhibits strong vaginal tropism, and IL-17A plays a critical role in controlling C. auris-associated VVC.