Cooperative Interactions between Trichomonas vaginalis and Associated Bacteria Enhance Paracellular Permeability of the Cervicovaginal Epithelium by Dysregulating Tight Junctions

Abstract

The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia). Both diseases are linked to the transmission of human immunodeficiency virus (HIV) and preterm birth, which complications are likely to result from the disruption of the cervicovaginal epithelial barrier. Here, we show that paracellular permeability of fluorescein isothiocyanate (FITC)-dextran through a monolayer of human ectocervical cells (hECs) is increased as a consequence of the activity of T. vaginalis and the aforementioned species of CST-IV bacteria cooperatively. T. vaginalis enhances paracellular permeability of hECs two times more than the individual bacterial species, by up to ∼10% versus ∼5%, respectively. However, any two or all three bacterial species are capable of synergizing this effect. T. vaginalis and the bacteria together increase the paracellular permeability of hECs by ∼50%, which is 5 to 10 times more than the results seen with the protozoan or bacteria alone. This effect is accompanied by enhancement of phosphatase activity, while phosphatase inhibition results in preservation of the integrity of the ectocervical cell monolayer. In addition, these microorganisms induce changes in the expression of tight junction proteins, particularly occludin, and of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Together, our findings establish that cooperative interactions between CST-IV bacteria and T. vaginalis enhance the paracellular permeability of the cervicovaginal epithelium by disturbing the integrity of the tight junction complex. Our study results highlight the importance of understanding the contribution of the vaginal microbiota to trichomoniasis.

Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2-3 among HPV16 positive female: a large population-based study.

“…In the vagina of female without BV, Gardnerella vaginalis was also detected, although it had a lower abundance and prevalence [33,34] . There was enormous substantial genetic diversity within Gardnerella vaginalis [16,35] , and virulence potential differentiate signi cantly between various genetic types/clades [15] ; this may correlate with the result in our study.…”

“…Hr-HPV (e.g. HPV 16,18,31,35,39,45,51,52,56,58,59,68,73,82) among them are associated with high grade cervical intraepithelial neoplasia and invasive cervical cancer.…”

Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2–3 among HPV16 positive female: a large population-based study

“…COBAS4800 (Roche Molecular Systems, Alameda, CA) assay was used for typing HPV DNA. The COBAS 4800 HPV test detected a total of 14 h-HPV types simultaneously: HPV-16 individually, HPV-18 individually, and pooled hr-HPV genotypes other than HPV 16 and 18 (31,33,35,39,45,51,52,56,58,59, 66 and 68), in addition to a separate high b-globin control.…”

“…Hr-HPV (e.g. HPV 16,18,31,35,39,45,51,52,56,58,59,68,73,82) among them are associated with high grade cervical intraepithelial neoplasia and invasive cervical cancer.…”

Neutrophil interactions with the sexually transmitted parasite Trichomonas vaginalis: implications for immunity and pathogenesis

“…One major factor in the broad spectrum of disease severity associated with trichomoniasis is likely to be the strain of parasite, because clinical isolates vary broadly in their ability to kill cervicovaginal and prostate epithelial cells in vitro [6]. However, host factors such as the individualized microbiome [21,22], and immune response most likely also play a role [7]. In particular, many of the aforementioned symptoms are linked to inflammation [10].…”