Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted pathogens worldwide. The host immune response induced by viral infection is cell-type specific. Little is known about the innate immune response to this virus in its natural host cells. In this study, we established an in vitro HSV-2 infection model with human cervical epithelial (HCE) cells. The viral infection was sufficient to induce expression of Toll-like receptors (TLRs), and Western blot and reporter assays suggest that HSV-2 infection leads to dramatic activation of the NF-kappa B signaling pathway. More importantly, our data provide direct evidence that the activation of NF-kappa B is required for the production of both IL-6 and IFN-beta induced by HSV-2 in HCE cells. Taken together, our results suggest the potential contributions of TLRs and a critical role of NF-kappa B in the innate immune response to HSV-2 in HCE cells. (C) 2008 Elsevier Inc. All rights reserved.