C. albicans β-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

VIGEZZI C; SOTOMAYOR CE; RODRIGUEZ EMILSE; MIRÓ MS; ANGIOLINI SC; ICELY PA

Tucumán

Congreso; LXVII Reunión annual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunologia SAI

Type I interferons (IFNs-I) have been traditionally associated with antiviral immune responses, however, their importance in host defence against fungal pathogens is being increasingly appreciated. C.albicans(Ca) is the main causative agent of Vulvovaginal Candidiasis(VVC), an inflammatory disease affecting 75% of healthy women in reproductive age at least once in their lifetime.Objective:This study aimed to determine whether Caimmune recognition triggers IFNs-I pathway in epithelial cells of the female genital tract (FGT) and its ability to modulate the local immune response during VVC development.Methods: We carried out two experimental strategies with: a) FGT cell line and b) mice model of VVC. a) Human cervical epithelial cell line (HeLa) was stimulated in vitrowithviable Ca-SC5314(5:1 ratio); Heat-Killed-Ca; Ca-FKS1.S645P(-glucan defective strain); Curdlan (-(1,3)-glucan, Dectin-1 agonist) and LPS(control) during 4h. IFNβ, IRF3 and IRF7 (molecules associated with IFNs-I signature) mRNA levels were measured by qPCR.b) Female C57BL/6 (WT) and IFN-α/β receptor 1 deficient (IFNAR-/-) mice on pseudo estrus phase(estradiol-treated) were inoculated intravaginally with 5x106 blastospores of Ca. The pattern of susceptibility to infection was evaluated in terms of local fungal burden in vaginal lavages (VL) obtained at day(D) 1, 2, 4 and 8 post infection (pi). Pro and anti-inflammatory cytokines (ELISA)as well also polymorphonuclear cells (PMNs) recruitment were determined in VL. Histological studies were performed in mice vaginas.Results: The results obtained with the in vitro model showed thatyeast-to-hypha switch ofCa and the exposure of-glucan in the fungal wall were able to activate IFNs-I pathway in epithelial cells of the FGT showing strong induction of IFNβ and IRF7mRNA (p