Toll-like receptors (TLRs) play a crucial role in regulating innate immune response to HSV-2 infection. Current studies on TLRs and viral infection have used either immuno-competent cells and/or murine systems. The innate immune pathway in response to this virus in its natural host cells remains unclear. We have established an in vitro HSV-2 acute infection model with Human cervical epithelial (HCE cells, the primary target and natural host cells for HSV-2) to investigate the role of TLRs-mediated innate immune response to HSV-2. In current study, we found that HSV-2 infection induced NF-kB reporter activity and expression of cytokines are TLR4-dependent. Knockdown experiments demonstrated that the adaptor molecules MyD88 and Mal of the TLRs signaling pathways are required in the HSV-2 induced TLR4-dependent NF-kB activation in HCE cells. Western blot assay suggested that knockdown of TLR4 decreased the phosphorylation of IRAK1 and inhibitor of NF-kB (IkB-a) upon HSV-2 infection. Finally, decreased expression of either TLR4 or MyD88/Mal alone or both significantly abolished productions of IL-6 and IFN-beta by ELISA analysis. Taken together, our results reveal for the first time that there exists the pathway via TLR4-Mal/MyD88-IRAK1-NF-kB axis in response to HSV-2 infection in its natural host cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.