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

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

Buenos Aires

Congreso; 18th International Congress on Infectious Diseases (ICID); 2018

Sociedad Argentina de Infectología

Candida albicans is the prevalent etiological agent in acute vulvovaginal candidiasis (VVC) and the severe chronic condition known as recurrent VVC. A critical role of local innate immunity in the defense and pathogenesis of vaginal infection by Candida is proposed. The recognition of β-glucans 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-glucan synthase enzyme, whose putative catalytic subunit is FKS1. Mutations in this domain lead to lower or defective production of β-glucans. Our aim was to evaluate the pathogenicity of different C. albicans strains with defective expression of β-glucans in a VVC mouse model, focusing in local innate immunity. The strains used in this study were: C. albicans fks1/fks1 S645P (homozygote) with a mutation in hot-spot 1 of FKS1 gene; C. albicans SC5314, parental strain; and C. albicans FKS1/fks1 R1361R/H (heterozygote), clinical isolate, with a 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 at day (D) 0 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-α levels (ELISA).The vaginal infection with C. albicans S645P showed similar CFU than parental strain SC5314 during the study; meanwhile intravaginal levels of IL-1β and TNF-α were significantly decreased (p