Induction of B7-H1 and B7-DC expression on airway epithelial cells by the Toll-like receptor 3 agonist double-stranded RNA and human rhinovirus infection: In vivo and in vitro studies

J Allergy Clin Immunol. 2008 May;121(5):1155-60. doi: 10.1016/j.jaci.2008.02.009. Epub 2008 Apr 18.

Abstract

Background: T-cell infiltration of the epithelium is a key feature of chronic rhinosinusitis and asthma. Viral infections are an important cause of disease exacerbations. We have found virus-induced expression of T cell-interacting ligands, B7 homolog costimulatory molecules, on airway epithelium.

Objective: We tested the ability of human rhinovirus (HRV) 16 and double-stranded RNA (dsRNA) to alter the expression of B7 homologs on human airway epithelial cells.

Methods: BEAS2B and primary human airway epithelial cells were exposed in vitro to dsRNA (25 microg/mL) or HRV-16, and then expression of cell-surface protein and mRNA for B7 homologs was assessed by means of flow cytometry and real-time PCR, respectively. Additionally, human subjects were infected with HRV-16 in vivo, and mRNA for B7 homologs was assessed by means of real-time PCR in fresh nasal epithelial cell scrapings obtained before and daily up to 4 days after infection.

Results: dsRNA exposure of BEAS2B and human primary bronchial epithelial cells resulted in increased levels of cell-surface and mRNA expression of B7-H1 and B7-DC but not B7-H2 or B7-H3. Exposure of primary cells to HRV-16 resulted in induction of cell-surface expression of B7-H1 and B7-DC. Pretreatment with fluticasone propionate failed to suppress the induction of B7-H1 and B7-DC. Nasal scrapings taken at the time of peak symptom scores (3 days) after infection of 6 human subjects with HRV-16 displayed selective induction of levels of mRNA for B7-H1 and B7-DC.

Conclusion: These data show that HRV-16 infection or exposure to dsRNA induces epithelial B7-H1 and B7-DC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / biosynthesis*
  • B7-1 Antigen / biosynthesis*
  • B7-H1 Antigen
  • Bronchi / immunology
  • Bronchi / virology
  • Cells, Cultured
  • Coculture Techniques
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Picornaviridae Infections / immunology*
  • Programmed Cell Death 1 Ligand 2 Protein
  • RNA, Double-Stranded
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis / immunology
  • Rhinitis / metabolism
  • Rhinitis / virology
  • Rhinovirus
  • Sinusitis / immunology
  • Sinusitis / metabolism
  • Sinusitis / virology
  • Th1 Cells / immunology
  • Toll-Like Receptor 3 / agonists*

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • RNA, Double-Stranded
  • RNA, Messenger
  • Toll-Like Receptor 3
  • Interferon-gamma