MMP-7 promotes host recovery and lung function to influenza virus infection (VIR2P.1016)

Abstract

Abstract Wound healing is a critical aspect of recovery from influenza virus-induced lung damage. However, relatively little attention has been given to the role of host recovery mechanisms in influenza virus pneumonia. MMP-7, or matrilysin, is produced in the airways following damage and is known to promote airway homeostasis and respiratory cell migration and differentiation, possibly via immunomodulatory processes. We hypothesized that MMP-7 is a critical factor in recovery from influenza infection for both airway damage repair and respiratory function. MMP-7-/- mice are more susceptible to PR/8 influenza infection, and, while showing weight loss similar to WT controls, succumb on days 8-13 after infection. MMP-7-/- lungs scored higher than WT lungs in both acute and chronic tissue damage measures on day 7 after infection by histology, demonstrating MMP-7’s ability to reduce tissue damage and limit tissue remodeling at peak disease. Curiously, MMP-7-/- BAL taken day 3 after infection have lower levels of IL-6, KC, and MIG than WT BAL. Plethysmographic respiratory analyses on days 8-11 showed MMP-7-/- mice to have slower breathing rates and exaggerated expiratory functions, suggesting a role for MMP-7 in promoting proper lung function during attempted resolution. This study provides evidence of the impact of a specific tissue remodeling protein on lung function and influenza disease outcome.