Upregulation of TLR7 and TLR3 gene expression in the lung early after respiratory syncytial virus infection of mice

Abstract:

[Objective] TLR7 and TLR3 (Toll-like receptor, TLR) are the two of important pattern recognition receptors (PRRs) that recognize the single-stranded (ss) RNA and double-stranded (ds) RNA of virus-origin leading to activation of cells, respectively. RSV (respiratory syncytial virus, RSV) could be recognized by both TLR7 and TLR3. The aim of this study was to investigate the kinetics and profile of lung TLR7 and TLR3 expression during the early phase of the pathogenesis of RSV infection, and to explore its correlation with pulmonary inflammatory response. [Methods] We intranasally inoculated BALB/c mice with live RSV to induce acute lung inflammation, and detected the lung expression of TLR7 and TLR3 mRNA by semiquantitative RT-PCR analysis at the indicated times on day 1 after RSV infection. We also measured the transcription factor nuclear factor-kappaB (NF-κB) protein expression with western blot assay in nuclear extracts. Lung tissue sections were stained with hematoxylin and eosin and examined under a light microscope to perform the histopathological examination. [Results] We found that RSV infection could rapidly upregulate the lung expression levels of both TLR7 and TLR3 gene in a time-dependent manner, furthermore, the response of TLR7 to RSV (1 h) was prior to that of TLR3 (4 h). The mice inoculated intranasally with RSV resulted in activation of NF-κB as soon as 4 h later in lung tissue. Moreover, RSV mediated early transcriptional responses of TLR7 and TLR3 were parallelling with the severe extent of RSV-induced pulmonary inflammation. [Conclusion] TLR7 and TLR3 were really involved in RSV-induced lung inflammation by detecting the viral RNA. This may allowed the infected organism to detect viral infections and initiate a proinflammatory response via multiple TLRs. This study may be useful in the development of tools to modulate the activities of therapeutic TLR ligands.