Evaluation of Innate Immune Mediators Related to Respiratory Viruses in the Lung of Stable COPD Patients

Background:Little is known about the innate immune response to viral infections in stable Chronic Obstructive Pulmonary Disease (COPD). Objectives: To evaluate the innate immune mediators related to respiratory viruses in the bronchial biopsies and lung parenchyma of stable COPD patients.Methods:We evaluated the immunohistochemical (IHC) expression of Toll-like receptors 3-7-8-9 (TLR-3-7-8-9), TIR domain-containing adaptor inducing IFN beta (TRIF), Interferon regulatory factor 3 (IRF3), Phospho interferon regulatory factor 3 (pIRF3), Interferon regulatory factor 7 (IRF7), Phospho interferon regulatory factor 7 (pIRF7), retinoic acid-inducible gene I (RIG1), melanoma differentiation-associated protein 5 (MDA5), Probable ATP-dependent RNA helicase DHX58 (LGP2), Mitochondrial antiviral-signaling protein (MAVS), Stimulator of interferon genes (STING), DNA-dependent activator of IFN regulatory factors (DAI), forkhead box protein A3(FOXA3), Interferon alfa (IFN alpha), and Interferon beta (IFN beta) in the bronchial mucosa of patients with mild/moderate (n= 16), severe/very severe (n= 1618) stable COPD, control smokers (CS) (n= 1612), and control non-smokers (CNS) (n= 1612). We performed similar IHC analyses in peripheral lung from COPD (n= 1612) and CS (n= 1612). IFN alpha and IFN beta were assessed in bronchoalveolar lavage (BAL) supernatant from CNS (n= 168), CS (n= 169) and mild/moderate COPD (n= 1612). Viral load, including adenovirus-B, -C, Bocavirus, Respiratory syncytial Virus (RSV), Human Rhinovirus (HRV), Coronavirus, Influenza virus A (FLU-A), Influenza virus B (FLU-B), and Parainfluenzae-1 were measured in bronchial rings and lung parenchyma of COPD patients and the related control group (CS).Results:Among the viral-related innate immune mediators, RIG1, LGP2, MAVS, STING, and DAI resulted well expressed in the bronchial and lung tissues of COPD patients, although not in a significantly different mode from control groups. Compared to CS, COPD patients showed no significant differences of viral load in bronchial rings and lung parenchyma.Conclusions:Some virus-related molecules are well-expressed in the lung tissue and bronchi of stable COPD patients independently of the disease severity, suggesting a "primed" tissue environment capable of sensing the potential viral infections occurring in these patients.