J Clin Med . Evaluation of Innate Immune Mediators Related to Respiratory Viruses in the Lung of Stable COPD Patients

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J Clin Med


. 2020 Jun 10;9(6):E1807.
doi: 10.3390/jcm9061807.
Evaluation of Innate Immune Mediators Related to Respiratory Viruses in the Lung of Stable COPD Patients


Silvestro E D'Anna ¹ , Mauro Maniscalco ¹ , Vitina Carriero ² , Isabella Gnemmi ³ , Gaetano Caramori ⁴ , Francesco Nucera ⁴ , Luisella Righi ⁵ , Paola Brun ⁶ , Bruno Balbi ³ , Ian M Adcock ⁷ , Maria Grazia Stella ⁸ , Fabio L M Ricciardolo ² , Antonino Di Stefano ³



Affiliations

• PMID: 32531971
• DOI: 10.3390/jcm9061807

Free article

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 = 18) stable COPD, control smokers (CS) (n = 12), and control non-smokers (CNS) (n = 12). We performed similar IHC analyses in peripheral lung from COPD (n = 12) and CS (n = 12). IFNα and IFNβ were assessed in bronchoalveolar lavage (BAL) supernatant from CNS (n = 8), CS (n = 9) and mild/moderate COPD (n = 12). 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.

Keywords: COPD pathology; COPD phenotypes; disability; innate immune response; outcome; viral load.