C. ALBICANS BETA-1,3-GLUCAN ACTIVATES TYPE I INTERFERONS PATHWAY IN EPITHELIAL CELLS OF THE FEMALE GENITAL TRACT WHICH MODULATES THE LOCAL IMMUNE RESPONSE IN VULVOVAGINAL CANDIDIASIS

RODRIGUEZ, EMILSE; ANGIOLINI, SOFÍA CARLA; VIGEZZI, CECILIA; MIRÓ, MARÍA SOLEDAD; ICELY, PAULA ALEJANDRA; SOTOMAYOR, CLAUDIA ELENA

Tucumán

Congreso; LXVII Reunion Anual de a Sociedad Argentina de Inmunología; 2019

Type I interferons(IFNs-I) function in fungal pathogenesis is little known. C. albicans (Ca) is causal agent of Vulvovaginal Candidiasis(VVC), an inflammatory disease affecting 75% of women worldwide. The aim was to study the fungal elements involved in IFNs-I pathway activation in epithelial cells of female genital tract (FGT) and its ability to modulate the local immune response during VVC development. Two experimental strategies were used: a) In vitro cultured of FGT cell and b) VVC murine model. Human cervical epithelial cells(HeLa) were stimulated with: viable Ca-SC5314(5:1 ratio); Ca-Heat-Killed; Ca-FKS1.S645P (-glucan defective strain); Curdlan (Dectin-1 agonist) and LPS(control) during 4h. IFNβ, IRF3 and IRF7 mRNA levels were measured by qPCR. Our results showed that yeast-to-hypha switch of Ca and the exposure of β-glucan in the fungal wall were able to activate IFNs-I pathway in epithelial cells showing strong induction of IFNβ and IRF7 mRNA (p<0.01). VVC model were developed in C57BL/6(WT) and IFN-α/β receptor 1 deficient (IFNAR-/-) mice after intravaginal inoculation of 5x106 Ca. The pattern of infection susceptibility was evaluated by local fungal burden(CFU), cytokines level(ELISA) and PMN recruitment in vaginal lavages, and histological scores(S)(Invasiveness-S and Inflammation-S) at day(D) 1, 2, 4 and 8 post infection. The results showed that in absence of IFNAR-mediated signalling initial vaginal fungal burden was high (D1p<0.05) and Invasiveness-S and Inflammation-S were increased (D2p<0.05). Local cytokine balance was modified and IL-1βwas lower in IFNAR-/- compared to WT animals (D2, D4p<0.001). Our results demonstrate that fungal b-glucan recognition is a relevant event for triggered IFNs-I pathway in FGT and early protective role for IFNs-I on VVC.