Transcriptomic Profiling of TSST-1–Induced Cytotoxicity and Inflammatory Responses in Human Vaginal Epithelial Cells

Objective Toxic shock syndrome toxin-1 (TSST-1) is a critical superantigen produced by certain staphylococcal strains, closely associated with menstrual toxic shock syndrome and mucosal inflammation. While the systemic superantigenic function of TSST-1 is well-established, its early cytotoxic and inflammatory effects on human vaginal epithelial cells (HVEC) remain poorly characterized. This study, therefore, seeks to investigate the initial temporal dynamics of TSST-1-induced cell viability, inflammatory cytokine responses, and barrier disruption in a model of human vaginal epithelium, along with a detailed analysis of the transcriptome. Methods We evaluated the impact of recombinant TSST-1 on HVEC at different doses and treatment durations. Subsequent exposure assessments included cell viability, apoptosis, and cell cycle distribution via flow cytometry, alongside inflammatory gene expression and transcriptomic profiling. Results TSST-1 could significantly reduce cell viability and proliferation in a dose- and time-dependent manner, accompanied by increased apoptosis and marked G1 phase arrest. In contrast, early exposure did not result in a uniform upregulation of all inflammatory mediators; rather, multiple cytokines exhibited dose-dependent segmented response patterns instead of a linear increase. RNA sequencing analysis of samples treated with 125 or 1000 ng/mL TSST-1 for 48 hours revealed extensive transcriptional reprogramming involving chemokine signaling, cytokine-receptor interactions, epithelial stress-related pathways, and metabolic rewiring. Notably, the number of differentially expressed genes induced by moderate-dose TSST-1 exceeded that of high-dose treatment, while high-dose TSST-1 specifically enriched pathways related to hypoxia and glycolysis. Conclusion These findings demonstrate that TSST-1 can trigger cytotoxicity, apoptosis, cell cycle disruption, and a graded inflammatory response in vaginal epithelial cells, providing a systematic transcriptomic framework for understanding the early mucosal responses induced by TSST-1.