Contribution Of fungal virulence factors and fungal recognition receptors in the regulation of the expression of human beta defensins 1 and 3

ANGIOLINI, SOFIA CARLA; RODRIGUEZ, EMILSE; MIRÓ, MARÍA SOLEDAD; ICELY, PAULA ALEJANDRA; SOTOMAYOR, CLAUDIA ELENA

Mar del Plata, Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

SAI, FAIC, SAIC, SAFIC

Acute vulvovaginal candidiasis (AVVC) is an inflammatory disease that affects up to 75% of women of childbearing age once in their lifetime, but 9% of them present a recurrent form of mycosis (RVVC) (>=8 episodes per year). Candida albicans (Ca) is the most prevalent agent, its main virulence factors are hyphal formation, adherence, hydrolytic enzyme generation and biofilm forming capacity (BFC). Human β-defensins 1 and 3 (hBDs) are cationic peptides with antimicrobial and chemoattractant activity. Our objective was to characterize the virulence pattern of Ca clinical isolates from AVVC and RVVC patients and the role of Ca virulence factors and innate recognition in the regulation of hBDs. BFC, lipase activity (LIP) and aspartylproteinases activity (SAP) of strains isolated from patients (CVVR=20 and CVVA=20), collection strains (SC5314 and ATCC36801) and β-glucan mutation (FKS1) were evaluated. Ca, heat-killed Candida (HKC) strains or fungal PAMPs agonists (LPS, Pam3CSK4, Zymosan,Curland) were added to HeLa cell cultures and modulation of hBDs 1 and 3 (2 or 4h) was determined by qPCR and protein expression (INCell Analyzer2500 HS). CVVR strains showed lower CBF than CVVA and Ca-SC5314 strains (p<0.05), while SAP activity was higher than in CVVA strains(p<0.05). Clinical strains were classified according to their virulence profile and used to stimulate HeLa cells. After 2h, HKC induced transcription of both BDs(p<0.05) and at 4h hBD1 and 3 mRNA were induced by strain FKS1. HKC and SC5314 strain increased hBD1 and CVVR isolates selectively increased hBD3. In addition, protein expression of hBDs was determined, by observing representative images of these immunofluorescences the response pattern of the stimuli used was evaluated. Knowledge of the virulence attributes of Ca and the role of RRPs exhibited during CVVR in the modulation of BDs is relevant for a better understanding of the pathogenesis of the disease and evaluating their potential use as therapeutic agents.