IL17 and Candida albicans colonization in the vaginal mucosa

Abstract

Abstract Candida albicans is a ubiquitous commensal fungus that colonizes human mucosal tissues. C. albicans can become pathogenic, clinically manifesting most commonly as oropharyngeal, dermal or vulvovaginal candidiasis (VVC). Studies in mice and humans convincingly show that Th17/IL-17-driven immunity is essential to controlling oral and dermal candidiasis. In contrast, the role of the IL-17 pathway during VVC remains controversial, with conflicting reports from human data and mouse models. It has been observed that a strong IL-17-related gene signature is induced in the vagina during estrogen (E2)-dependent murine VVC. IL-17R deficient mice are resistant to VVC in this standard model of E2-induced disease. Since estrogen increases susceptibility to vaginal colonization and subsequent immunopathology, first we asked whether its use in the standard VVC model masks a role for the Th17/IL-17 axis. Here, we demonstrate that mice lacking IL-17 receptor signaling showed no evidence for altered VVC susceptibility or immunopathology, regardless of estrogen administration, supporting the emerging consensus that Th17/IL-17 axis signaling is dispensable for the immunopathogenesis of VVC. We further considered the epithelial dynamics during murine VVC. C. albicans colonizes mucosal epithelial tissues, particularly those expressing Keratin 13 (K13). When estrogen levels are high, this epithelium becomes increasingly keratinized, characterized by a thick layer of thin, flat pieces of tissue. In order to visualize the expression patterns in the vaginal epithelium, we developed a reporter mouse where LACZ is expressed in all tissues containing K13. We present data using these mice to assess epithelial dynamics during VVC.