title: Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Baylor College of Medicine, Houston, Tex., USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Singh
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Lee
authors.forename: Paul
authors.initials: P
authors.lastname: Porter
authors.forename: Chuang
authors.initials: C
authors.lastname: Xu
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohno
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Greenberg
authors.forename: Venkata
authors.initials: V
authors.lastname: Bandi
authors.forename: Jim
authors.initials: J
authors.lastname: Gern
authors.forename: Svetlana
authors.initials: S
authors.lastname: Amineva
authors.forename: Alex
authors.initials: A
authors.lastname: Aminev
authors.forename: Tim
authors.initials: T
authors.lastname: Skern
authors.forename: Pamela
authors.initials: P
authors.lastname: Smithwick
authors.forename: Sarah
authors.initials: S
authors.lastname: Perusich
authors.forename: Nadia
authors.initials: N
authors.lastname: Barrow
authors.forename: Luz
authors.initials: L
authors.lastname: Roberts
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000008:administration & dosage* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D011014:Pneumonia; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology* / Q000821:virology; D012229:Rhinovirus / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014764:Viral Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus