Abstract
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 IFNβ (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 (IFNα), and Interferon beta (IFNβ) 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). IFNα and IFNβ 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.
Highlights
Inflammation plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD) [1,2,3]
We have shown that some viral-related molecules, such as RIG1, melanoma differentiation-associated protein 5 (MDA5), LGP2, Stimulator of interferon genes (STING), and dependent activator of IFN regulatory factors (DAI), are well expressed in the lung tissue and bronchi of both stable Chronic Obstructive Pulmonary Disease (COPD) at different stages of disease severity and control subjects, in the presence of low levels of respiratory viruses in both bronchial rings and lung parenchyma
The cytokines (IFNα, IFNβ) commonly involved in the anti-viral response are expressed at low levels in the bronchial mucosa, lung parenchyma, and in the bronchoalveolar lavage (BAL) fluid of both stable COPD patients and control groups
Summary
Inflammation plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD) [1,2,3]. The innate immune system recognizes the microbial pathogens through pattern-recognition receptors (PRRs), which detect the pathogen-associated molecular patterns (PAMPs) of bacterial, fungal, and viral origin [4,5] This interaction induces a cascade of events generating inflammatory host responses and the activation of adaptive immune responses [4,5]. 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 IFNβ (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 (IFNα), and Interferon beta (IFNβ) in the bronchial mucosa of patients with mild/moderate (n = 16), severe/very severe (n = 18) stable COPD, control smokers (CS) (n = 12), and control non-smokers (CNS) (n = 12). 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
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