摘要目的 探讨白细胞介素17A(IL-17A)在小鼠呼吸道合胞病毒(respiratory syncytial virus,RSV)感染中的作用.方法 6～8周龄雌性野生型C57BL/6小鼠及IL-17A敲除(IL-17A-/-)小鼠各自按随机数字表分为对照组和RSV组,分别滴鼻接种细胞培养上清或RSV A2病毒液.部分小鼠灌取支气管肺泡灌洗液(BALF)并行炎症细胞计数及分类计数;部分小鼠取左肺,HE染色后行组织病理评分;全身体积描记法检测小鼠肺功能;酶联免疫吸附试验(ELISA)检测IFN-γ水平;空斑试验检测RSV病毒滴度.为进一步证实IL-17A与IFN-γ的关系及其在RSV感染中的作用,部分IL-17A-/-小鼠经腹腔注射给予外源性重组IL-17A或重组IFN-γ,部分野生型小鼠经腹腔注射给予特异性IFN-γ单克隆抗体.结果 RSV感染后,两种小鼠相比,野生型小鼠BALF中炎症细胞总数、中性粒细胞计数、淋巴细胞计数,气道高反应性,肺组织病理损伤程度、病理评分,IFN-γ水及肺组织中RSV病毒滴度均明显高于IL-17A-/-小鼠.RSV组IL-17A-/-小鼠补充外源性重组IL-17A或重组IFN-γ 后,IFN-γ水平明显升高,BALF中炎症细胞计数、气道高反应性、肺组织病理损伤明显增加,外源性重组IL-17A处理后病毒清除显著减少,而外源性重组IFN-γ处理后病毒清除不受影响.RSV组野生型小鼠特异性中和IFN-γ后,BALF中炎症细胞计数、气道高反应性、肺组织病理损伤明显减轻,但病毒清除不受影响.结论 IL-17A可能通过促进IFN-γ产生或抑制RSV病毒清除,参与RSV感染后致病.

abstractsObjective To identify the role of IL-17A during respiratory syncytial virus (RSV) in-fection in a mouse model. Methods Female wild-type C57BL/6 mice and IL-17A knockout ( IL-17A-/-) mice at the age of 6 to 8 weeks were both randomly divided into two groups:control and RSV groups. Mice in the control groups were given the supernatant of Hep-2 cell culture, while those in the RSV groups were treated with RSV A2 through intranasal administration. Leukocytes in bronchoalveolar lavage fluid ( BALF) samples were counted. Left lung tissues were stained with hematoxylin and eosin ( HE ) to evaluate his-topathological scores. Airway hyperresponsiveness ( AHR) was measured by whole-body plethysmography. The concentrations of IFN-γ were determined with ELISA. RSV titers were measured by plaque assay. To assess the effects of IL-17A on IFN-γproduction and its role in RSV infection, IL-17A-/- mice were treated with exogenous recombinant murine IFN-γ or IL-17A, while wild-type mice were given IFN-γ neutralizing antibody intervention. Results The counts of inflammatory cells and neutrophils in BALF, lung tissue his-topathological scores, AHR, IFN-γlevels and virus titers of the wild-type group were higher than those of the IL-17A-/-group after RSV infection. IFN-γlevels, inflammatory cell counts in BALF, AHR and lung tissue histopathological scores were significantly increased in RSV-infected IL-17A-/- mice after the intervention of recombinant murine IL-17A or IFN-γ. RSV titers were much higher in the recombinant murine IL-17A-trea-ted group, but not affected by the recombinant murine IFN-γ intervention. Inflammatory cell counts in BALF, AHR and lung tissue histopathological scores were significantly decreased in RSV-infected wild-type mice following IFN-γ neutralizing antibody treatment, but no significant changes were found in RSV titers. Conclusions IL-17A might be involved in the pathogenesis of pulmonary diseases during RSV infection through promoting IFN-γ production and inhibiting viral clearance in mice.