Clinical Candida albicans strain downregulates human anti microbial peptide Beta Defensin 1 in vitro and in patients with Recurrent Vulvovaginal Candidiasis

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

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) are two forms of a disease that affects a large number of otherwise healthy women. Innate immune responses by the epithelium, including antimicrobial peptides (AMP) are critical for protection against Candida albicans (Ca) overgrowth. β-Defensin 1 (BD1) is important for control of early mucosal Ca infection. The aim of this study was to evaluate BD1 expression and regulation in patients with acute (AVVC) and the recurrent form of this mycosis. Inclusion criteria were: otherwise healthy women of at least 18 years of age, diagnosed with at least three microbiologically tested episodes of VVC within one year (RVVC group) or with a single episode (AVVC group). Healthy women were included as Control group. Patients Cervicovaginal lavage (CVL) was obtained from all participants by instilling 3 ml of sterile saline into the posterior vagina. The cells recovered from CVL were used for RNA extraction or fixed for immunofluorescence (IF) staining against BD1. For In Vitro assays a cervical human epithelial cell line (HeLa) was incubated with: Ca recovered from a RVVC patient (Ca-RVVC), Ca SC5314 collection strain at different fungus/cell ratios (1:1, 5:1), heat killed Ca (HKC) and Zymozan (Zym) for 4 hr, and BD1 expression (Flow Cytometry) was evaluated. BD1 transcripts from CVL recovered cells were diminished in RVVC patients when compared to Controls. Also, BD1 protein expression (IF) was downregulated in this group of patients compared to Control and AVVC group. HeLa cells incubated with Ca-RVVC showed a diminished expression of the protein (5:1 ratio) (p<0,05), meanwhile Ca SC5314, HKC and Zym didn?t promote changes, indicating that pathogenic Ca strain is capable of downregulate the expression of BD1 in human epithelial cells. This is the first report that demonstrates that BD1 is downregulated in epithelial cells from RVVC patients, but not in AVVC patients, indicating an important role for this AMP in the disease.