Date Published: June 6, 2019
Publisher: Public Library of Science
Author(s): José García-Valero, Jordi Olloquequi, Juan F. Montes, Esther Rodríguez, Mireia Martín-Satué, Laura Texidó, Jaume Ferrer Sancho, Aran Singanayagam.
COPD patients are prone to acute infectious exacerbations that impair their quality of life and hamper prognosis. The purpose of the present study was to investigate the in situ IFN-β response in the lungs of stable COPD and non-COPD patients. Lung samples from 70 subjects (9 control never smokers, 19 control smokers without COPD, 21 patients with moderate COPD and 21 patients with very severe COPD) were studied for the expression of IFN-β, its main transcription factor, IRF-7, and two products of its autocrine function, namely RIG-I and MDA-5, by immunohistochemical techniques and quantitative real-time PCR. IFN-β, IRF-7, RIG-I and MDA-5 were widely detected in most lung cell types. In epithelial tissues and alveolar macrophages, IFN-β and IRF-7 labeling scores were decreased up to 65% and 74%, respectively, for COPD patients, paralleling an analogous reduction (43% and 65%, respectively) in the amount of their lung mRNA. Moreover, this decreased production of IFN-β in COPD patients correlated with a similar decrease in the expression of RIG-I and MDA-5, two essential members of the innate immune system. Our study indicates that most lung cells from stable COPD patients show a constitutive decreased expression of IFN-β, IRF-7, RIG-I and MDA-5, suggesting that this deficiency is the main cause of their acute viral exacerbations.
Current understanding about what role risk factors, other than tobacco, play in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) is still incomplete [1–3]. In this regard, recent results clearly emphasize the importance of respiratory infections, the imbalance of lung microbiome, and host-microorganism interactions in fueling the progression of chronic lung diseases, including asthma and COPD [4–6].
IFNs are cytokines expressed by most cells that regulate many different biologic functions, including the inflammatory and immune responses . Type I IFN-β, playing a critical role in the regulation of innate immunity, is secreted abundantly in response to viral infection in nearly all cell types. Recently, it has been demonstrated  that IFN-β is also secreted constitutively in low amounts to induce a local state of alertness which assures rapid and efficient antiviral responses.