Increased susceptibility of Caspase-1 deficient mice to vaginal infection with a low virulent Candida albicans strain.

RODRIGUEZ, EMILSE; MIRÓ, MARÍA SOLEDAD; VIGEZZI, CECILIA; CEJAS, HUGO; ICELY, PAULA ALEJANDRA; SOTOMAYOR, CLAUDIA ELENA

Buenos Aires

Congreso; LXIII Argentinian Immunology Society Meeting; 2015

Argentinian Immunology Society

Candida albicans is causal agent of Vulvovaginal candidiasis(VVC). Immunopathogenic response in VVC is governed by innate immune mediators. NLRP3-inflammasome activation by fungal components induces Caspase-1 activation, which cleaves proIL-1β into biologically active cytokine. Herein, we aimed to study the contribution of Caspase-1 pathway in the local response against attenuated virulence(AV) C.albicans strain(Ca) in a model of VVC. Ca ATCC-36801(Virulent-V) and AV-ATCC-36801 were used. Female C57BL/6(WT) and Caspase-1-/- mice in estrus phase (estradiol treated) were intravaginally inoculated with 5.106 Ca at day(D) 0. Estrogenized(E) and untreated mice were included as controls. At D2,4 and 8 of infection, vaginal lavage(VL) was obtained to evaluate the cell type present, fungal burden(CFU) and cytokine levels(ELISA) and vaginas and lumbar ganglia for histological studies. After Ca-V infection in WT-animals, VL was characterized by the presence of PMNC. The infection remained through the evaluated days; fungal forms were present in lumen and stratum corneum and associated with PMNC infiltrate and intraepithelial abscesses. The IL-1β was significantly diminished (D8) compared with WT-E group(p<0,05). No change in TNF-alpha and TGF-beta were detected. WT-animals infected with AV-Ca strain showed a low fungal burden (D2,D4)(p<0,05) and complete clearance at D8. In Caspase-1-/- mice infected with AV-Ca strain, the CFU were higher than WT-infected with same strain (D2,D4p<0,05), but similar to WT-mice infected with Ca-V. Vaginas of Caspase-1-/- showed moderate PMNC infiltrate and ganglion reactivity with frequent histocytes and leucocytes in marginal sinus. The increased susceptibility of Caspase-1 deficient mice to C.albicans infection illustrates its critical role in host defense during CVV.