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

RODRIGUEZ EMILSE; VIGEZZI C; MIRÓ MS; ICELY PA; SOTOMAYOR CE

Mar del Plata

Congreso; LXVI Reunión annual de la Sociedad Argentina de Inmunologia y LXI Sociedad Argentina de Investigación Clínica; 2018

SAI , SAIC

Candida 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. Theaim 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 different morphotypes of Ca SC5314 strain:Invasive Ca (hypha emission) and Non-invasive Ca (pseudomicelio) at different fungus:cell ratio (0.25:1, 5:1);Ca DNA complexed with polyethylenimine (Ca-DNA), LPS and Poly I:C during 4 and 24h.IFNb, IRF3, IRF7 and Mx1 mRNA levels were measured by qPCR.Poly I:C (24h) and LPS (4h) were able to induce a strong IFNb mRNA expression in HeLa cells(p<0,001). Unexpectedly, InvasiveCa triggers an early IFNbexpression(4h)(p<0,001) involving high levels of IRF7(p<0,01). Activation of the IFNAR receptor, evidenced by an increase of Mx1 expression, occurs after 24h(p<0,05).It was also observed that non-invasive Cainduced similar levels of IFNb mRNA than the invasive morphotype at 4h(p<0,001), however, it continued to be able to induce significant levels at 24h(p<0,001). High IRF7and Mx1 mRNAexpression were observed(p<0,001).The increase in the expression of the genes studied was dependent on the fungus:cell ratio.Interestingly, Ca-DNA induced IFNb at 24h(p<0,001) with an increase in IRF3 expression(p<0,001). However, it was not possible to observe Mx1 induction at the time evaluated.These results provide important and novel evidence about the ability of Candida albicansto activate the IFNs-I pathway in epithelial cells of the female genital tract.