Vulvovaginal Candidiasis: contribution of the beta-glucan receptor Dectin-1

MIRÓ, MARÍA SOLEDAD; RODRIGUEZ, EMILSE; VIGEZZI, CECILIA; ICELY, PAULA ALEJANDRA; RIERA, FERNANDO OSCAR; CAEIRO, JUAN PABLO; SOTOMAYOR, CLAUDIA ELENA

Curitiba

Congreso; 15th INFOCUS; 2017

Introduction:Candida albicans is a common commensal of mucosal surfaces and the most frequentcause of vulvovaginal candidiasis (VVC). The pathology affects 75% of all women atleast once during their lifetime. Approximately 9% experience recurrent episodes ofVVC (RVVC). This distressing condition is characterized by more than four episodes ofVVC per year. Nowadays it is proposed that there is most likely a genetic componentthat contributes to the onset of RVVC. Pattern recognition receptors, such as Dectin-1,are essential determinants of host antifungal immunity. Dectin-1 is a major β-glucanreceptor expressed on the surface of a variety of cells. This receptor recognizes β-1,3-glucans that are exposed on many fungi, including species of Candida.Objective:In this work we aimed to evaluate the susceptibility to vaginal Candida infection inDectin-1 Knockout (Dectin-1-/-) mice, focusing in the study of the early interactionsbetween the fungus and local innate immune mechanisms.Methods:Female C57BL/6 mice (WT) and Dectin-1-/- were treated with estradiol on days (D) -6, -3, 2, 4 and were intravaginally inoculated with 5.106 C. albicans SC5314 (D0) or onlytreated with estradiol (control). On D2, 4 and 8 vaginal lavages (VL) were performed tostudy the presence of different cell populations, fungal burden (CFU), IL-1β, TNF-α, IL17,IL-22 and IL-23 levels (ELISA) and vaginas were removed, sectioned and stained forhistological analysis (PAS).Results:Dectin-1-/- mice were susceptible to the vaginal infection with higher CFU at D2 pi, anda progressive fungal burden reduction through D8, but without differences with WTmice. IL-1β, regarded as the hallmark of VVC immunopathogenesis, and TNF-α levels inVL were increased in infected animals of both strains, compared with controls duringall evaluated D (p<0,05). While in WT mice IL-1β decreased by D8, this phenomenonwas not seen in Dectin-1-/- mice. IL-17, IL-22 and IL-23 were not detected in VL.Histological studies showed a higher presence of invasive morphotype in the stratumcorneum of Dectin-1-/- mice, especially at D8 pi, compared with WT mice. The tisularresponse was characterized by inflammatory cells forming intraepithelialmicroabscesses.Conclusion:Taken altogether, these results show that the innate receptor Dectin-1 doesn?tcontribute to the control of vaginal fungal burden during VVC. However, the geneticdisruption of Dectin-1 favored the fungus invasion to vaginal mucosa, fact thatcan lead to an increase production of IL-1β, worsening the symptoms of the disease.