Trichomonas vaginalis-shaped inflammatory microenvironment drives macrophage immune signaling and modulates cervical cancer cell proliferation and migration

Background Trichomonas vaginalis (TV) infects more than 275 million individuals annually worldwide. However, the effects of the TV-induced inflammatory microenvironment on macrophage immune signaling and cervical cancer cell behavior remain unclear. Here, we investigated macrophage responses to the in vitro TV-induced inflammatory milieu and evaluated its effects, with or without macrophages, on cervical cancer cell proliferation and migration. Methods We characterized cytokine profiles and their associated signaling pathways in macrophages after short- and long-term exposure to conditioned medium from TV-stimulated ectocervical cells (TCM). Additionally, the roles of TCM-enriched IL-6, CXCL-1, and IP-10 in regulating TCM-activated pathways were validated. Furthermore, the effects of TCM and the conditioned medium from TCM-stimulated THP-1 macrophages (T-TCM) on HeLa cell proliferation and migration were investigated. Results Short-term stimulation of THP-1 macrophages with TCM significantly increased the secretion of SCGF-β and G-CSF, while suppressing IP-10 production. In contrast, prolonged TCM exposure led to elevated levels of G-CSF, IP-10, IL-1ra, and IL-6. Mechanistically, short-term TCM stimulation enhanced activation of the PI3K, STAT3, and NF-κB signaling pathways, promoting the release of SCGF-β, G-CSF, and IP-10. Conversely, long-term TCM stimulation markedly activated the PI3K, STAT1, and p38 MAPK pathways, leading to increased secretion of IP-10, IL-1ra, and IL-6 but decreased G-CSF production. Moreover, TCM treatment enhanced HeLa cell proliferation and migration, whereas T-TCM exerted suppressive effects on these processes. Conclusions Collectively, our findings provide novel insights into the immunomodulatory roles of the TV-induced inflammatory microenvironment in shaping macrophage immune signaling cascades and influencing cervical cancer cell behavior.