Differential Responses of Murine Vaginal and Uterine Epithelial Cells Prior to and Following Herpes Simplex Virus Type 2 (HSV‐2) Infection

PROBLEM: This study was undertaken to evaluate the susceptibility of upper and lower reproductive tract epithelial cells (ECs) to herpes simplex virus type 2 (HSV-2) infection and examine their cytokine secretion patterns prior to and following infection. METHOD OF STUDY: Primary EC cultures, grown from murine vaginal and uterine tissue, were inoculated with HSV-2. Viral shedding was measured in apical and basolateral compartments. Multi-analyte bead-based immunoassays run on Luminex, were used to analyse cytokine profiles. RESULTS: Both vaginal and uterine ECs became productively infected with HSV-2, ex-vivo. Uterine ECs displayed varying degrees of infection, dependent on transepithelial resistance of the monolayers. Co-culturing stromal cells did not significantly change levels of viral shedding from ECs. Uterine ECs and epithelial-stromal co-cultures constitutively secreted interleukin (IL)-1alpha, IL-6, mouse homologue of human IL-8 (KC) and monocyte chemotactic protein-1 (MCP-1), while vaginal epithelial-stromal co-cultures secreted granulocyte-macrophage colony stimulating factor (GM-CSF) and KC. Following exposure to HSV-2, IL-6 and MCP-1 levels decreased in uterine EC cultures. CONCLUSIONS: This data shows that ECs from the upper and lower reproductive tract have different cytokine secretion profiles and respond differentially to infection. HSV-2 may be able to suppress epithelial cytokine secretion as a strategy to evade host immune system.