Nystatin enhances the immune response against Candida albicans and protects the ultrastructure of the vaginal epithelium in a rat model of vulvovaginal candidiasis

Xu Zhang,Zhaohui Liu,Suxia Wang,Ting Li,Xi Chen

doi:10.1186/s12866-018-1316-3

Abstract

BackgroundVulvovaginal candidiasis (VVC) is a common infectious disease of the lower genital tract. Nystatin, a polyene fungicidal antibiotic, is used as a topical antifungal agent for VVC treatment. The aim of the current study was to investigate the possible immunomodulatory effects of nystatin on the vaginal mucosal immune response during Candida albicans infection and examine its role in protection of vaginal epithelial cell (VEC) ultrastructure.ResultsFollowing infection with C. albicans, IFN-γ and IL-17 levels in VECs were significantly elevated, while the presence of IgG was markedly decreased as compared to uninfected controls (P < 0.05). No significant differences in IL4 expression were observed. After treatment with nystatin, the level of IFN-γ, IL-17 and IgG was dramatically increased in comparison to the untreated group (P < 0.05). Transmission electron microscopy revealed that C. albicans invades the vaginal epithelium by both induced endocytosis and active penetration. Nystatin treatment protects the ultrastructure of the vaginal epithelium. Compared with the untreated C. albicans-infected group, Flameng scores which measure mitochondrial damage of VECs were markedly decreased (P < 0.001) and the number of adhesive and invasive C. albicans was significantly reduced (P < 0.01) after treatment with nystatin.ConclusionsNystatin plays a protective role in the host defense against C. albicans by up-regulating the IFN-γ-related cellular response, the IL-17 signaling pathway and possibly through enhancing VEC-derived IgG-mediated immunity. Furthermore, nystatin notably improves the ultramorphology of the vaginal mucosa, partially through the protection of mitochondria ultrastructure in VECs and inhibition of adhesion and invasion by C. albicans. Together, these effects enhance the immune response of the vaginal mucosa against C. albicans and protect the ultrastructure of vaginal epithelium in VVC rats.

Highlights

Vulvovaginal candidiasis (VVC) is a common infectious disease of the lower genital tract
Following an intravaginal inoculation with C. albicans, > 1 × 105 Candida colony-forming units (CFU)/mL were detected 1 h post infection and the number slightly declined to 9 × 104 CFU/mL 4 d post infection (Fig. 3c)
Our present study shows that healthy vaginal epithelial cells (VECs) express low levels of IFN-γ, IL-4 and IL-17

Summary

Introduction

Vulvovaginal candidiasis (VVC) is a common infectious disease of the lower genital tract. The aim of the current study was to investigate the possible immunomodulatory effects of nystatin on the vaginal mucosal immune response during Candida albicans infection and examine its role in protection of vaginal epithelial cell (VEC) ultrastructure. Interferon-gamma (IFN-γ) is a type II IFN produced by activated T cells, natural killer (NK) cells and natural killer T cells [9] It activates phagocytes and favors the development of a Th1 protective response that participates in the clearance of fungal pathogens [10]. IL-17 has emerged as an essential mediator of protection against C. albicans in oral and dermal candidiasis [12] It promotes antifungal immunity through up-regulation of pro-inflammatory cytokines, neutrophil-recruiting chemokines and antimicrobial peptides, which limit fungal overgrowth [13]. We speculate that Th2/Th1 balance may be related with antifungal activity against C. albicans

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