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

• Published in: Journal of allergy and clinical immunology Vol. 121; no. 5; pp. 1155 - 1160
• Main Authors: Heinecke, Lowella, Proud, David, Sanders, Scherer, Schleimer, Robert P., Kim, Jean
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.05.2008; Elsevier; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Antigens, CD - biosynthesis; Asthma; B7 homologs; B7-1 Antigen - biosynthesis; B7-H1 Antigen; Biological and medical sciences; Bronchi - immunology; Bronchi - virology; cell-surface molecules; Cells, Cultured; Coculture Techniques; costimulatory ligands; Cytokines; double-stranded RNA; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - virology; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; human airway epithelial cells; Human subjects; Humans; Immune system; Immunopathology; Infections; Interferon-gamma - metabolism; Ligands; Lymphocytes; Male; Medical sciences; Middle Aged; Picornaviridae Infections - immunology; Programmed Cell Death 1 Ligand 2 Protein; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis - immunology; Rhinitis - metabolism; Rhinitis - virology; Rhinovirus; rhinovirus infection; RNA, Double-Stranded; RNA, Messenger - analysis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sinusitis - immunology; Sinusitis - metabolism; Sinusitis - virology; Th1 Cells - immunology; Toll-Like Receptor 3 - agonists; Viral infections; dsRNA; CRS; rhinovirus infection; B7 homologs; double-stranded RNA; JHMIRB; HRV; DMEM; PBEC; TCID 50; human airway epithelial cells; PNEC; cell-surface molecules; HBSS; costimulatory ligands; Chronic rhinosinusitis; Primary bronchial epithelial cell; Johns Hopkins Medicine Institutional Review Board; Human rhinovirus; Dulbecco modified Eagle medium; Hanks' balanced salt solution; Tissue culture infective dose; Primary nasal epithelial cell; Agonist; Double stranded RNA; Toll like receptor 3; Picornaviridae; Ligand; Respiratory system; Cell surface; Respiratory tract; Immunology; B7 molecule; Rhinovirus; Human; Immunopathology; Induction; In vitro; Costimulatory molecule; Virus; Infection; In vivo; Epithelial cell; B7-H1 molecule
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2008.02.009

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. 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. BEAS2B and primary human airway epithelial cells were exposed in vitro to dsRNA (25 μg/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. 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. These data show that HRV-16 infection or exposure to dsRNA induces epithelial B7-H1 and B7-DC.