Innate immune receptors involved in the pathogenesis of Vulvovaginal Candidiasis

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

Curitiba

Congreso; XII Forum on Fungal Infection in the Clinical Practise; 2014

Candida albicans is the main opportunistic pathogen found in patients with vulvovaginal candidiasis (VVC), a fungal infection affecting more than 75% of all childbearing women at least once in their lifetime. Approximately 8% experience recurrent episodes of VVC (RVVC). This distressing condition is characterized by more than three episodes of VVC per year. Nowadays it is proposed that there is most likely also a genetic component that contributes to the onset of RVVC. In this work we aimed to evaluate the susceptibility to vaginal Candida infection in mice strains with different immune genetic background focusing our studies in the contribution of innate immune receptors involved in the pathogen component recognition. Female TLR2-/- (Knock out, KO-animals), MYD88-/- and C57BL/6 (WT) mice were used in this study. Estrus phase was induced by estradiol injections. Infected animals were intravaginally inoculated with 5.106 C. albicans ATCC-36801 at day(D) 0. Treated-uninfected mice were included as controls. At different D of infection, vaginal lavage was obtained to evaluate fungal burden(CFU) and cytokine levels(ELISA); vaginas were removed for histological studies(HE,PAS). At D2 fungal burden in TLR2-KO was higher than WT and MYD88-KO mice (p<0,05). Pro-inflammatory cytokines IL-1β and IL-6, in TLR2-KO and only IL-1β, in MYD88-KO animals were increased compared to controls (p<0,05), while they remained unchanged in WT. Histological studies acording to the presence of PMNC and fungal?s invasiveness score showed a major inflammation and presence of the pathogen in TLR2-KO compared with others strains. At D4, TLR2-KO showed less fungal burden than WT and MYD88-KO mice (p<0,05), and a remarcably increased inflammation and invassivenes. At D8 MYD88-KO mantained iqual levels of vaginal fungal burden than at D4 while in WT and TLR2-KO it was diminished, reveling that MYD88- KO animals weren?t able to resolve the infection. Ours results demonstrate that fungal recognition through TLR2 and the activation pathway triggered by this innate receptor would not be relevant during VVC. We also provide evidence that MYD88, a crucial adapter protein involved in the intracellular signaling downstream several innate receptors, such as TLR7, TLR9 and others plays an important role in the resolution of this disease.