Human rhinovirus proteinase 2A induces T(H)1 and T(H)2 immunity in patients with chronic obstructive pulmonary disease

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Background: 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. Objective: We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors. Methods: 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. Results: 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 T(H)1 and T(H)2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong T(H)1 and T(H)2 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-gamma production from CD4 T cells. Conclusion: Our findings suggest that patients with severe COPD show T(H)1- and T(H)2-biased responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a T(H)1- and T(H)2-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. (J Allergy Clin Immunol 2010;125:1369-78.)
Publisher
MOSBY-ELSEVIER
Issue Date
2010-06
Language
English
Article Type
Article
Keywords

NONTYPABLE HAEMOPHILUS-INFLUENZAE; ALLERGIC AIRWAY INFLAMMATION; RESPIRATORY VIRUSES; EXPERIMENTAL ASTHMA; VIRAL-INFECTIONS; CELL EGRESSION; LUNG-DISEASE; EXACERBATIONS; INTERLEUKIN-5; POLARIZATION

Citation

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, v.125, no.6, pp.1369 - 1378

ISSN
0091-6749
URI
http://hdl.handle.net/10203/174442
Appears in Collection
MSE-Journal Papers(저널논문)
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