Toll-like Receptor 3 Mediated Inflammatory Response To Respiratory Syncytial Virus

Respiratory syncytial virus (RSV), an enveloped, non-segmental, negative-stranded RNA virus and a member of the family paramyxoviridae, is the major cause of serious lower respiratory tract infections in infancy and early childhood and is also becoming widely recognized as an important pathogen in the elderly and in immunosuppressed adults. RSV, entrying into the host respiratory epithelium by cell surface fusion, induces the expression and/or secretion of proinflammatory and immunomodulatory mediators. Severe RSV infection involves the release of inflammatory mediators, epithelial cell necrosis, inflammation, and mucus production. The discovery of TLRs has revolutionized our understanding of RSV-induced respiratory tract inflammatory disease.Toll-like receptors, type I integral membrane proteins, very important receptors to identify pathogens, are central to early host defense. They detect bacterial, viral and environmental exposures and activate both innate and adaptive immune responses. Recent studies indicate that Toll-like receptor 3 is the specific receptor for double stranded RNA, a common intermediate in the reproductive cycle of many viruses. It has been found that TLR3 signal transduction pathway is involved in activating of airway epithelial cells,with secreting a large number of cytokine related to inflammatory and immune,which plays an important role in the development and process of pneumonia. Up to now, its mechanism is so complex that there is no satisfactory treatment. Accordingly, it has very important medical significance to deep research the mechanism of RSV infection. Objective To investigate the expression changes of TLR3 on human lung epithelial cells (A549) and mouse lung infected with RSV. To study the relationships between TLR3 signal transduction pathway and it mediated inflammatory response to RSV.Methods We observed the effects of RSV infection on TLR3 signal transduction pathway in A549 cells and in mouse lung by evaluating the expression of TLR3 mRNA by semiquantitative RT-PCR. The expression of NF-κB activity was detected by Western-Blot using nuclear protein. The expression of TNF-αmRNA and protein were measured by semiquantitative RT-PCR and ELISA, respectively.Results RSV infection significantly up-regulates the transcription of TLR3 mRNA and TNF-αmRNA. In accordance with the expression of TLR3, RSV stimulation induces the activation of NF-κB. RSV infection also enhances TNF-αproduction not only in cell culture supernatant but also in mouse serum. The changes of each index vary significantly (P<0.01) compared with the control group.Conclusions RSV infection could up-regulate the expression of TLR3. The inflammatory response to RSV may associate with the TLR3 signal transduction pathway. TLR3 could mediate the NF-κB activation and induce exceeded expression of TNF-α.