IL-17A involved in respiratory syncytial virus-associated pathogenesis by promoting IFN-γ and inhibiting viral clearance in mice

Objective To identify the role of IL-17A during respiratory syncytial virus (RSV) infection 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 histopathological 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-γ production 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 histopathological scores, AHR, IFN-γ levels and virus titers of the wild-type group were higher than those of the IL-17A-/- group after RSV infection. IFN-γ levels, 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-treated 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. Key words: Respiratory syncytial virus (RSV); IL-17A; IFN-γ; Viral clearance