Sneathia vaginalis and Sneathia sanguinegens elicit conserved inflammatory responses in a human 3D cervical cell model.

Sneathia species are emerging pathogens associated with adverse gynaecologic, obstetric and neonatal sequelae, including bacterial vaginosis, preterm birth, chorioamnionitis, non-gonococcal urethritis and HPV-mediated cervical carcinogenesis. Yet, their pathogenicity is poorly understood due to their fastidious nature. Here, we conducted infection assays using multiple strains of Sneathia vaginalis and Sneathia sanguinegens to evaluate host responses in an in vitro 3D organotypic model of the human cervix. We profiled a broad array of proteins, including antimicrobial peptides, cytokines, growth factors, mucins, matrix metalloproteinases and proteins related to apoptosis and cellular stress. Both Sneathia species induced similar pro-inflammatory signatures. Notably, all strains robustly induced IL-6 and IL-8/CXCL8 (P from 0.02 to <0.0001), which are clinical markers associated with preterm birth, vaginal dysbiosis and cervical carcinogenesis. Most strains also induced the two chemokines IP-10/CXCL10 and MIP-3α/CCL20. Conversely, no significant induction of matrix metalloproteinases or apoptosis-related proteins was observed. Furthermore, co-infection with both species elicited similar cytokine patterns with no synergistic effects observed. Collectively, investigation of multiple strains confirms that both Sneathia species trigger a conserved immune-mediated response. This reveals a shared pathogenic mechanism that represents a potential pathway toward adverse gynaecologic and obstetric outcomes.