beta-glucan composition in Candida albicans wall is relevant to promote inflammatory reaction during the curse of vulvovaginal Candidiasis.

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

Congreso; 18th International Congress on Infectious Disease; 2018

Candida albicans is the prevalent etiological agent in acute vulvovaginal infection and the severe chronic condition known as recurrent vulvovaginal candidiasis (VVC). A critical role of local innate immunity in defense and pathogenesis of vaginal infection by Candida is proposed. The recognition of -glucan by the innate immune receptor Dectin-1, is essential during antifungal immunity. β-1,3-glucans exposed on C.albicans wall are synthesized by β-1,3-glucans glucan synthase enzyme, whose putative catalytic subunit is FKS1. Mutations in this domain lead to lower or defective production of -glucans. Our aim was to evaluate the pathogenicity of different C.albicans strains with defective expression of -glucan cell wall in VVC mouse model, focusing in local innate immunity.Methods and materials:The strains used in this study were: C.albicans fks1/fks1 S645P (homozygote) with mutation in hot-spot 1 of FKS1 gene; C. albicans SC5314, parenteral strain; and C.albicans FKS1/fks1 R1361R/H (heterozygote), clinic isolated, with mutation in hot-spot 2 of FKS1 gene. Female C57BL/6 mice were treated with estradiol and were intravaginally inoculated with 5.106 C.albicans of different strains (D0) or only treated with estradiol. On D2, 4 and 8 vaginal lavages (VL) were performed to study fungal burden (CFU) and proinflammatory cytokines IL-1β and TNF levels (ELISA).Results:The vaginal infection with C.albicans S645 showed similar CFU than parenteral strain SC5314 during the study; meanwhile intravaginal levels of IL1β and TNF were singnificantly decreased (p<0.001). The infection with C. albicans R1361R/H (hot spot 2 mutation) was maintained during all study, and the CFU at D2 were significant higher than C.albicans SC5314 (p<0.01). Interestingly, the mutated strain only triggered the local production of IL1 (p<0.05), but the levels were significantly lower compared with animals infected C.albicans SC5314 at D2(814 vs 435 pg/ml; p< 0.05) and at D4 (784 vs 342 pg/ml; p<0.01) of infection. Not changes were observed in TNF levels.Conclusion:Taken altogether, these results show the relevant contribution of b-glucans of C.albicans wall in the activation of local innate immune mediators, providing a new evidence about the fungal element involved in the pathogenesis of CVV.