Interaction of Gardnerella vaginalis and Vaginolysin with the Apical versus Basolateral Face of a Three-Dimensional Model of Vaginal Epithelium

• Published in: Infection and immunity 2019-04, Vol.87 (4)
• Main Authors: Garcia, Erin M, Kraskauskiene, Vita, Koblinski, Jennifer E, Jefferson, Kimberly K
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - metabolism; Bacterial Toxins - metabolism; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Epithelium - microbiology; Female; Gardnerella vaginalis - genetics; Gardnerella vaginalis - growth & development; Gardnerella vaginalis - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; Interleukin-18 - genetics; Interleukin-18 - metabolism; Vagina - microbiology; Vagina - pathology; Vaginosis, Bacterial - genetics; Vaginosis, Bacterial - metabolism; Vaginosis, Bacterial - microbiology; Vaginosis, Bacterial - pathology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00646-18

Studies have implicated as an important etiological agent in bacterial vaginosis (BV). It produces a cholesterol-dependent cytolysin, vaginolysin (VLY). In this study, we sought to characterize the interaction between vaginal epithelium, , and VLY using EpiVaginal tissues from MatTek. These tissues are three-dimensional and have distinct apical and basolateral sides, enabling comparison of the effects of and VLY following exposure to either side. We measured cytotoxicity, cytokine production, and bacterial growth, following apical versus basolateral exposure. exhibited more-rapid growth in coculture with the tissue model when it was exposed to the apical side. VLY permeabilized cells on the basolateral side of the tissues but failed to permeabilize apical epithelial cells. Cytokine secretion in response to VLY and also depended on the polarity of exposure. VLY did not cause significant changes in cytokine levels when exposed apically. Apical tissue challenge by appeared to dampen the inflammatory response, as decreases in granulocyte-macrophage colony-stimulating factor (GM-CSF) (6.6-fold), RANTES (14.8-fold), and interferon gamma inducible protein 10 kDa (IP-10) (53-fold) and an increase in interleukin-1 receptor antagonist (IL-1ra) (5-fold) were observed. , normally colonizes the apical face of the vaginal epithelium. Results from this study suggest that while may grow on the apical face of the vaginal epithelium, its VLY toxin does not target these cells in this model. This phenomenon could have important implications regarding colonization of the vagina by and may suggest an explanation for the lack of an overt immune response to this organism.