Herpes Simplex Virus 2 infection up‐regulates TLRs expression and activates NF‐kB in human cervical epithelial cells

Abstract

Toll‐like receptors (TLRs) play a crucial role in the innate immune response against microbial infections, engaging differential signaling pathways, leading to activation of T cell and therefore triggering acquired immunity. Herpes Simplex Virus type 2 (HSV‐2) is one of the most common sexually transmitted pathogen and can establish lifelong latency infection. HSV‐2 is a significant co‐factor in the transmission and acquisition of HIV‐1. To determine the effect of HSV‐2 infection on TLRs expression pattern and to investigate the TLR‐mediated innate immune reponse to HSV‐2 in human cervical cells, we infected immortalized human cervical epithelial cells (HECs) with HSV‐2 (G strain) as a model in this study. The results showed that normal HECs expressed TLR1, 2, 3, 4,5, 6,9 and HSV‐2 infection up‐regulated TLRs expression at mRNA and protein level. TLR9 was dramatically elevated at late phage 36hr post‐infection by Real‐time RT‐PCR analysis. The NF‐kB and MAP Kinase p38 were rapidly activated as early as 1hr post‐infection. Different proinflammatory cytokines and interferons were also determined during the course of HSV‐2 infection. Thus, HECs possess the ability to sensor HSV‐2 infection and activate the host innate immune response through TLRs.This work was supported by grants from the National Natural Science Foundation of China (No. 30500465) and China Wuhan Chenguang Science Foundation.