Pulmonary C-fiber degeneration downregulates IFN-γ receptor 1 via IFN-α induction to attenuate RSV-induced airway hyperresponsiveness

• Published in: Virology (New York, N.Y.) N.Y.), 2017-10, Vol.510, p.262-272
• Main Authors: Ye, Zhixu, Ren, Luo, Tang, Zhengzhen, Deng, Yu, Xie, Xiaohong, Fu, Zhou, Luo, ZhengXiu, Xu, Fadi, Zang, Na, Liu, Enmei
• Format: Article
• Language: English
• Subjects: Airway hyperresponsiveness; Animals; Disease Models, Animal; Down-Regulation; Host-Pathogen Interactions; IFN-α; IFN-γ; IFN-γ receptor; Interferon gamma Receptor; Interferon-alpha - metabolism; Mice, Inbred BALB C; Nerve Fibers, Unmyelinated - metabolism; Pulmonary C-fiber; Receptors, Interferon - biosynthesis; Respiratory Hypersensitivity; Respiratory Syncytial Virus Infections - pathology; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Viruses - immunology; RSV
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2017.06.034

Respiratory syncytial virus (RSV) is a leading cause of respiratory infection in infants. Unfortunately, no effective vaccine or treatment against RSV is currently available. Pulmonary C-fibers (PCFs) are critical for regulating pulmonary inflammation and airway hyperresponsiveness (AHR). We previously reported that IFN-γ partially mediated RSV-induced airway disorders. In this study, we found that PCF degeneration alleviated RSV-induced airway inflammation, especially AHR by downregulating IFN-γ receptor 1 (IFNGR1), but had no effect on IFN-γ induction. In contrast, PCF degeneration actually increased IFN-α/β levels, as were the levels of STAT1 and phosphorylated STAT1 (pSTAT1). Exogenous IFN-α treatment induced STAT1 activation and downregulated IFNGR1 expression. These results suggest that PCFs affect IFNGR1 expression by inducing IFN-α to regulate IFN-γ-mediated airway inflammation and AHR. Thus, targeting PCFs activation may help control RSV-induced airway disorders, especially AHR, even with the presence of inflammation. [Display omitted] •PCFs degeneration alleviates RSV-induced airway inflammation, especially AHR.•PCFs regulate RSV-induced IFN-γ receptor, but have no effect on IFN-γ induction.•PCFs degeneration increases RSV-induced IFN-α/β induction and decline virus titer.•PCFs degeneration downregulates RSV-induced IFNGR1 via IFN-α induction.