Pulmonary C‐Fibers (PCFs) Are Essential for Airway Inflammation (AI) and Hyperreactivity (AHR) Induced by Respiratory Syncytial Virus (RSV) Infection

Abstract

RSV infection causes acute AI and AHR with the peak response occurring at ~5th day postinfection (PID 5) in humans and animals. Owing to the critical role of PCFs in regulating pulmonary inflammation and airway resistance, we tested the contribution of PCFs to these RSV‐induced disorders. These RSV‐induced disorders are reportedly dependent on increased IFN‐γ in our previous study. IFN‐γ could activate C‐fibers and the latter affect the production of the former. Thus, we asked whether PCFs were required in IFN‐γ upregulation by RSV and the IFN‐γ‐mediated AI and AHR. RSV and mock were instilled intranasally in PCF‐intact (CON) and PCF‐degenerated (KPCF) mice. On PID 5, we measured specific airway resistance (sRaw) in awake state and collected lung tissues after euthanasia for detecting BALF inflammatory cells, the lung viral titration, substance P (SP), IFN‐γ and its transcription factor (T‐bet) gene expressions. Compared with CON, KPCF mice showed significant decreases in: (1) weight loss and RSV titer in the lungs; (2) total cells and macrophages in BALF with little change in lymphocytes; (3) inflammatory cells infiltrated in the lungs; (4) the sRaw response to aerosol of methacholine (3.125 ‐ 50 mg/ml); and (5) SP. In addition, the augmented IFN‐γ and T‐bet by RSV infection was not significantly different between the two groups of mice. However, recombinant IFN‐γ (ip) induced AHR in the CON, but not KPCF mice. Our results suggest that PCFs play an important role in RSV replication, the RSV‐induced AI and AHR. Moreover, PCFs were required for IFN‐γ‐promoted AI and AHR (Supported by HL119683).