Candida albicans activates type I interferon pathway in cells of the female genital tract

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

Congreso; LXVI Annual Meeting of Sociedad Argentina de Inmunología; 2018

C. albicans (Ca) is an opportunistic fungal pathogen that typically exists as a harmless commensal in the female genital tract; however, approximately 75% of women who are of reproductive-age suffer from vulvovaginal candidiasis(VVC) at least once in their lifetime. Recent studies revealed that, besides viruses and bacteria, fungal pathogens can also induce type I interferons (IFNs-I) production by innate immune cells. The aim was to study whether Ca recognition induces IFNs-I in epithelial cells of female genital tract in order to establish a possible role during VVC. For this purpose, human cervical epithelial cell line (HeLa) were stimulated with: Ca SC5314 strain as Invasive Ca (hypha emission) and Non-invasive Ca (pseudomicelio) (0,25:1 fungus:cell ratio); Ca DNA complexed with polyethylenimine (Ca-DNA), LPS and Poly I:C during 4 and 24h. IFN, IRF3, IRF7 and MX1 (IFNAR receptor activation marker) mRNA levels were measured by qPCR. A comparative analysis was made between 4 and 24h. LPS (4h) and Poly I:C (24h) were able to induce a strong IFN mRNA expression in HeLa cells(p<0,001). Interestingly, Invasive Ca triggered an early IFN expression (4h) (p<0,001) involving high levels of IRF7(p<0,01) and IRF3(p<0,05). Non-invasive Ca induced similar levels of IFN and IRF7 at 4h(p<0,001), but, it was also able to induce IFN expression at 24h(p<0,05). Both stimuli showed a higher Mx1 expression at 24h(p<0,05), however, invasive Ca induced a 10-fold increase(p<0,05). Ca-DNA induced IFN at 24h(p<0,001) with high IRF3 expression(p<0,001). However, it was not possible to observe Mx1 induction at the time evaluated. Studies performed in vaginal lavage cells of patients with Recurrent VVC showed that 50% expressed high levels of IFN mRNA while Acute VVC patients did not. These results provide important and novel evidence about the ability of C. albicans to activate the IFNs-I pathway in epithelial cells of the female genital tract.