IL-17A involved in respiratory syncytial virus-associated pathogenesis by promoting IFN-γand inhib-iting viral clearance in mice / 中华微生物学和免疫学杂志

ABSTRACT

Objective 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 groupscontrol 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.