Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease

• Published in: Journal of allergy and clinical immunology Vol. 125; no. 6; pp. 1369 - 1378.e2
• Main Authors: Singh, Manisha, Lee, Seung-Hyo, Porter, Paul, Xu, Chuang, Ohno, Ayako, Atmar, Robert L., Greenberg, Stephen B., Bandi, Venkata, Gern, Jim, Amineva, Svetlana, Aminev, Alex, Skern, Tim, Smithwick, Pamela, Perusich, Sarah, Barrow, Nadia, Roberts, Luz, Corry, David B., Kheradmand, Farrah
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2010; Elsevier; Elsevier Limited; American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc
• Subjects: Adult; Aged; Allergies; Animals; Biological and medical sciences; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cells, Cultured; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Cysteine Endopeptidases - administration & dosage; Cysteine Endopeptidases - pharmacology; Dendritic Cells - drug effects; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Interferon-gamma - metabolism; Interleukin-4 - metabolism; lung inflammation; Lymphocyte Activation - drug effects; Male; Medical sciences; Mice; Mice, Inbred C57BL; Middle Aged; Picornaviridae Infections - complications; Picornaviridae Infections - immunology; Picornaviridae Infections - virology; Pneumology; Pneumonia; proteinase; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - virology; Respiratory diseases; Rhinovirus - enzymology; Rhinovirus - immunology; Rhinovirus - pathogenicity; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Th1 Cells - immunology; TH1/TH2 cells; Th2 Cells - immunology; Viral infections; Viral Proteins - administration & dosage; Viral Proteins - pharmacology; GOLD; AE; MoDC; TH1/TH2 cells; BAL; HRV; LES-COPD; proteinase; PC200; OVA; chronic obstructive pulmonary disease; lung inflammation; COPD; DC; Picornaviridae; Lung; Th1 lymphocyte; Helper cell; Respiratory system; Immunity; Human rhinovirus; Immunology; T; 2 cells; T-Lymphocyte; Bronchus disease; Chronic obstructive pulmonary disease; Th2 lymphocyte; Rhinovirus; Human; Lung disease; Immunopathology; Enzyme; Respiratory disease; Inflammation; Virus; Peptidases; 1/T; Hydrolases
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.02.035

Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide. Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease. We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors. Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103). We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions. We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice. HRVs are isolated from nasal and lung fluid from subjects with AE-COPD. Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells. Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells. Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD. Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD.