Divergent Effects of Trichomonas vaginalis on Cervical Cancer Cells HPV-positive and HPV-negative: Interplay with Purinergic Signaling.

Trichomonas vaginalis is the protozoan that causes trichomoniasis, the most common non-viral sexually transmitted infection in the world. Recently, studies have highlighted the possible association between T. vaginalis and the development of cervical cancer, as well as co-infection with human papillomavirus (HPV), suggesting a role of the protozoan in oncogenesis. In the cervical cancer context, the purinergic signaling influences immunosuppression and angiogenesis, while high concentrations of adenosine can induce cell death. T. vaginalis uptakes adenosine for survival as well it takes advantage in its immunomodulatory effects. Thus, the presence of T. vaginalis could influence cell survival, modulating the tumor microenvironment. Our study demonstrated that, in ex vivo models, T. vaginalis increased cell proliferation, immune infiltrate, and vascularization. Meanwhile, in in vitro 2D cell culture models, T. vaginalis combined with purinergic signaling differentially affects the viability of HPV-positive (SiHa) and HPV-negative (C33A) cervical cancer cell lines, with significant impact in the cell line without HPV. The ATP and adenosine signaling did not affect the cytotoxicity exerted by conditioned medium against both cell lines. T. vaginalis reduced the IL-6 production and E6 oncogene expression by SiHa cells. the Ki-67 gene expression was modulated by the parasite and ATP/adenosine metabolism, highlighting the plasticity of the purinergic signaling combined with the parasite. These findings indicate that T. vaginalis exerts cytotoxicity and modulation of pathways relevant to the tumor microenvironment, influencing cell death, inflammation, and tissue remodeling processes, and shed light to further studies on the interactions between T. vaginalis and host cells.