Mucosal Immunol. 2025 Jul 10:S1933-0219(25)00072-8. doi: 10.1016/j.mucimm.2025.07.001. Online ahead of print.
ABSTRACT
Vulvovaginal candidiasis (VVC) is a mucosal infection predominantly caused by Candida albicans, affecting over three-quarters of immunocompetent women worldwide. While the female genital tract mucosa is the primary defense against the fungus, the specific immune mechanisms involved in this host-pathogen interaction remain largely unknown. In this study, we explored the relevance of type-I interferons (IFNs-I) pathway using both in vitro and in vivo models of VVC. Our quantitative proteomic analysis revealed that C. albicans induces the activation of the IFNs-I pathway in human epithelial cells (ECs) of the female genital tract shortly after exposure to the fungus. Additionally, we identified β-glucans as a crucial fungal component involved in triggering this pathway. Using a VVC model in IFN-α/β receptor-deficient (Ifnar1-/-) mice, we demonstrated that IFNs-I regulate the fungal burden, C. albicans epithelial invasion, polymorphonuclear neutrophils (PMNs) recruitment, inflammatory tissue response, local cytokine balance, and the composition of T cell subsets in the draining lymph nodes. These findings underscore the pivotal role of the IFNs-I pathway in ECs-mediated responses against C. albicans, especially in the early stages of VVC development, offering insights into potential therapeutic targets for this condition.
PMID:40651511 | DOI:10.1016/j.mucimm.2025.07.001