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

Severe respiratory infections are often associated with ALI/ARDS [17] [18] [19] , and the pathophysiology is similar for a variety of infectious pathogens. For example, patients with SARS and MERS-CoV were found to have increased infiltration of inflammatory macrophages, accumulation of debris in the lung, and diffuse alveolar damage [20, 21] . Similarly, elderly patients suffering from RSV sustained widespread alveolar damage [22] . Bacterial pneumonia can result in increased formation of hyaline membranes [23] . Deposition of collagen and fibrin, while necessary for lung repair, can also build up and block gas exchange [24] . In the case of influenza, the major complication leading to ALI/ARDS is pulmonary edema and impaired fluid clearance due to dysregulation of transporters that clear fluid from the alveolus such as ENaC and Na + K + ATPase [23, 25, 26] . The virus itself can also directly kill epithelial cells [27] . ALI/ ARDS has a mortality rate of 30-50%, therefore it is critical from a public health perspective to understand the mechanisms at play [28, 29] .