科研之友
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摘要
Objective: To prove that immune escape is involved in the pathogenesis of respiratory syncytial virus (RSV) by inhibiting Toll-like receptor (TLR) signaling pathway. Methods: We established a rat model with nephropathy induced by RSV for different days (4, 8, 14, 30, 60, 90, 120 d) to seek the evidence of RSV immune escape in kidney, lung and spleen tissues as well as PBMCs, meanwhile, the expressions of TLR3, TLR4 and NF-kappa B, IFN-gamma and IL-13, RSV fusion (RSV-F) protein as well as 24 h urine protein were compared and analyzed via real time fluorescent quantitative PCR detection, indirect immunofluorescent assay, ELISA and flow cytometry, to explore the correlations between persistent RSV infection and the immune response mediated by TLR and its signaling pathway. Results: RSV continuously survived in kidney, lung and spleen for 120 days. The expressions of TLR3, NF-kappa B and IL-13 in each group changed with the RSV infection time: compared with the normal healthy rats, their expressions were significantly increased on day 4, 14, 90 and 120 after the virus inoculation when the expression of RSV was at high level, (P<0.05); however, when RSV survived at a low-replication level, TLR3 was obviously inhibited (P>0.05). Moreover, TLR4 and IFN-gamma expressions had no significant difference compared with the control group (P>0.05), except that TLR4 had a significant increase on day 4 and an apparent reduction on day 60, while IFN-gamma elevation on Day 4 and 14. In addition, 24 h urine protein increased gradually and peaked at day 60. Conclusion: The continuous infection of RSV mainly suppressed the immune response via inhibiting the TLR4, TLR3 and IFN-gamma signal pathway, indicating that the suppression of TLR4 and TLR3 signal pathways might be an essential mechanism of RSV immune escape, therefore RSV could continuously infect the body via immune escape, which is an important link of causing T-cell dysfunction and minimal change nephritic syndrome.
