Vaginal Epithelial Cells Discriminate Between Yeast and Hyphae of Candida albicans in Women Who Are Colonized or Have Vaginal Candidiasis

• Published in: The Journal of infectious diseases Vol. 220; no. 10; pp. 1645 - 1654
• Main Authors: Roselletti, Elena, Perito, Stefano, Sabbatini, Samuele, Monari, Claudia, Vecchiarelli, Anna
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08.10.2019
• Subjects: Adult; Asymptomatic; c-Fos protein; Candida albicans; Candida albicans - growth & development; Candidiasis; Candidiasis, Vulvovaginal - pathology; Carrier State - immunology; Cell Survival; Commensalism; Enzyme-linked immunosorbent assay; EphA2 protein; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - microbiology; Epithelial Cells - physiology; Erythropoietin; Female; FUNGI; Hepatoma; Humans; Hyphae; Hyphae - growth & development; Immunologic Factors - analysis; L-Lactate dehydrogenase; Lactic acid; Liver cancer; Middle Aged; NF-κB protein; Pattern recognition receptors; Pseudohyphae; TLR2 protein; TLR4 protein; Toll-like receptors; Transcription activation; Transcription factors; Vagina; Vagina - microbiology; Womens health; Young Adult; inflammation; pseudohyphae; hyphae; p-p38; c-Fos; human vaginal candidiasis; epithelial cells; yeast; C. albicans
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz365

Abstract Background Vaginal candidiasis is common disease affecting women; however, how Candida albicans shift from commensalism towards a pathogenic status remains poorly understood. The present study investigated the vaginal epithelial cell (EC) response dynamics under various conditions. Methods Healthy women, asymptomatic C. albicans carriers, and symptomatic patients with vaginal candidiasis were enrolled in this study. ECs in vaginal swabs were analyzed with cytofluorimetric analysis for pattern recognition receptors and intracellular signals, with lactate dehydrogenase assay performed for cell damage, and an enzyme-linked immunosorbent assay for cytokine expression. Results The level of toll-like receptor 4 (TLR4), TLR2, and erythropoietin-producing hepatoma A2 (EphA2) expression was significantly higher in ECs from asymptomatic and symptomatic subjects compared to healthy subjects. Activation of transcription factors, nuclear factor-κB (NF-κB) and c-Fos–p-38, was observed in ECs from symptomatic and asymptomatic pseudohyphae/hyphae carriers but not from the asymptomatic yeast carriers. EC damage was only observed in symptomatic patients. Conclusions The presence of pseudohyphae/hyphae is required to determine vaginal candidiasis; however, it may be not sufficient to induce the pathologic process associated with neutrophil recruitment and EC damage. This study sheds light on the ambiguous role of the hyphal form during vaginal human commensalism. We investigated the role of human epithelial cells during asymptomatic C. albicans colonization or symptomatic vaginal candidiasis. This study identified several immune parameters that discriminate between commensalism versus pathogenicity, suggesting that pseudohyphae and hyphae can cohabit during the saprophytic status.