An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens

Meliopoulos, Victoria A.; Van de Velde, Lee-Ann; Van de Velde, Nicholas C.; Karlsson, Erik A.; Neale, Geoff; Vogel, Peter; Guy, Cliff; Sharma, Shalini; Duan, Susu; Surman, Sherri L.; Jones, Bart G.; Johnson, Michael D. L.; Bosio, Catharine; Jolly, Lisa; Jenkins, R. Gisli; Hurwitz, Julia L.; Rosch, Jason W.; Sheppard, Dean; Thomas, Paul G.; Murray, Peter J.; Schultz-Cherry, Stacey

At each breath, the lung is challenged by a large number and diversity of microbes and other foreign material such as pollen and dust. Many inhaled microbes cause lethal infections if not contained by the lung immune system, which has evolved to balance rapid and efficient microbial clearance with protection of the delicate lung structure from excessive damage. Lung damage caused by microbial pathogens is the cause of acute lung injury (ALI), which leads to increased edema, alveolar permeability, and impaired oxygen exchange. In severe cases, ALI can result in impaired gas exchange function and ultimately death (acute respiratory distress syndrome or ARDS) [1] . To mitigate lung damage after infection, inflammation resolves, returning to homeostasis that restores normal lung function [2, 3] . The air-interface structure of the lung involves a complex immune cell population including resident interstitial macrophages and dendritic cells, and GM-CSF-dependent alveolar macrophages [4] [5] [6] [7] . A key question in understanding pulmonary immunity concerns how the balance between effective immune surveillance and maintenance of lung anatomy and physiology is achieved through life.