The Effect And Mechanism Of Airway Inflamation And Airway Hyperresponsiveness In Athymic Nude Mice With Respiratory Syncytial Virus Infection

Objective:To establish a murine model of athymic nude mice with respiratory syncytial virus (RSV) infection and investigate the effect of T lymphocyte deficient on airway inflammation and airway hyperresponsiveness (AHR).Methods:Specific pathogen free6-8-week-old female athymic nude mice and BALB/c mice were divided into control group and RSV group randomly. After anesthetization, mice were intranasally inoculated with1.5×108PFU/ml RSV or with DMEM culture medium in a volume of100μl intranasally. On the3rd,5th,7th and14th days after innoculation, AHR was assessed. The total cells and differential white cell counts in bronchoalevolar lavage fluid (BALF) were tested. Pulmonary histopathology was assessed after hematoxylin-eosin staining. Cytokines from BALF were analysed by ELSIA. On the5th day, mRNA quantities of M2muscarinic receptor (M2R) and Toll like receptor3(TLR3) were detected by Q-PCR, etc.Results:RSV titer was higher and lasts longer in lungs of nude mice compared with BALB/c mice. RSV-infected mice had higher total cells, histopathologic score (HPS) than control groups. RSV-infected mice had decreased macrophage numbers and increased lymphocyte numbers (P<0.05) compared to control groups. H&E staining shown that inflammatory cells inflitrated in peribronchiole, peri vascular tissue and alveolitis. This inflammation lasts longer in lungs of BALB/c mice. AHR in both nude RSV group and BALB/c RSV groups are higher than control groups. AHR in BALB/c RSV group measured on5th day post infection reached the higest and displayed significant differences (P<0.05) with nude mice at that time. IFN-γ increased sharply in BALB/c RSV group, while had nearly no change in nude mice after RSV infection. TLR3mRNA expression was increased in nued mice after infection, but cytokines (such as IL-4, IL-10) and M2R mRNA expression altered little.Conclusion:The copies of RSV lasts longer in nude mice but had shorter lung inflammation period. AHR in nude mice is significantly lower than BALB/c RSV group and so is the level of IFN-y in BALF. This suggested inflammation and AHR after RSV infection are not totally parallel. T lymphocyte and its cytokines (such as IFN-y) might play important roles in the airway inflammatory pathologies post RSV infection.