TY - JOUR
T1 - Respiratory syncytial virus infection of airway epithelial cells, in vivo and in vitro, supports pulmonary antibody responses by inducing expression of the B cell differentiation factor BAFF
AU - McNamara, P S
AU - Fonceca, A M
AU - Howarth, D
AU - Correia, J B
AU - Slupsky, J R
AU - Trinick, R E
AU - Al Turaiki, W
AU - Smyth, R L
AU - Flanagan, B F
PY - 2013/1
Y1 - 2013/1
N2 - BACKGROUND: The mechanisms regulating antibody expression within the human lung during airway infection are largely unknown. In this study, our objectives were to determine if infection with respiratory syncytial virus (RSV) upregulates expression of the B cell differentiation factors A proliferation inducing ligand (APRIL) and B cell activating factor of the TNF family (BAFF), if this is a common feature of viral airway infection, and how this is regulated in human airway epithelial cells.METHODS: We measured BAFF and APRIL protein expression in bronchoalveolar lavage (BAL) fluid from infants with severe RSV disease, and healthy control children, and in nasopharyngeal aspirates from preschool children with other single respiratory viral infections. We also measured mRNA expression in bronchial brushings from RSV-infected infants, and in RSV-infected paediatric primary airway epithelial cell cultures (pAEC). Beas-2B cell cultures were used to examine mechanisms regulating BAFF expression.RESULTS: BAFF protein and mRNA were elevated (in marked contrast with APRIL) in BAL and bronchial brushings, respectively, from RSV-infected infants. BAFF protein was also found in upper airway secretions from children with human metapneumovirus, H1N1, bocavirus, rhinovirus, RSV and Mycoplasma pneumoniae infection. BAFF mRNA and protein were expressed following in vitro RSV infection of both pAEC and Beas-2B cultures, with mRNA expression peaking 12-h postinfection. BAFF induction was blocked by addition of a neutralising anti-interferon-β antibody or palivizumab.CONCLUSIONS: BAFF, produced through an interferon-β-dependent process, is a consistent feature of airway infection, and suggests a role for the airway epithelia in supporting protective antibody and B cell responses in the lung.
AB - BACKGROUND: The mechanisms regulating antibody expression within the human lung during airway infection are largely unknown. In this study, our objectives were to determine if infection with respiratory syncytial virus (RSV) upregulates expression of the B cell differentiation factors A proliferation inducing ligand (APRIL) and B cell activating factor of the TNF family (BAFF), if this is a common feature of viral airway infection, and how this is regulated in human airway epithelial cells.METHODS: We measured BAFF and APRIL protein expression in bronchoalveolar lavage (BAL) fluid from infants with severe RSV disease, and healthy control children, and in nasopharyngeal aspirates from preschool children with other single respiratory viral infections. We also measured mRNA expression in bronchial brushings from RSV-infected infants, and in RSV-infected paediatric primary airway epithelial cell cultures (pAEC). Beas-2B cell cultures were used to examine mechanisms regulating BAFF expression.RESULTS: BAFF protein and mRNA were elevated (in marked contrast with APRIL) in BAL and bronchial brushings, respectively, from RSV-infected infants. BAFF protein was also found in upper airway secretions from children with human metapneumovirus, H1N1, bocavirus, rhinovirus, RSV and Mycoplasma pneumoniae infection. BAFF mRNA and protein were expressed following in vitro RSV infection of both pAEC and Beas-2B cultures, with mRNA expression peaking 12-h postinfection. BAFF induction was blocked by addition of a neutralising anti-interferon-β antibody or palivizumab.CONCLUSIONS: BAFF, produced through an interferon-β-dependent process, is a consistent feature of airway infection, and suggests a role for the airway epithelia in supporting protective antibody and B cell responses in the lung.
KW - B-Cell Activating Factor/genetics
KW - Bronchiolitis/physiopathology
KW - Bronchoalveolar Lavage
KW - Case-Control Studies
KW - Cells, Cultured
KW - Child
KW - Epithelial Cells/metabolism
KW - Female
KW - Gene Expression Regulation
KW - Humans
KW - In Vitro Techniques
KW - Infant
KW - Infant, Newborn
KW - Interferon-gamma/genetics
KW - Male
KW - RNA, Messenger/metabolism
KW - Respiratory Syncytial Virus Infections/diagnosis
KW - Respiratory Syncytial Viruses/immunology
KW - Sensitivity and Specificity
KW - Severity of Illness Index
KW - Tumor Necrosis Factor Ligand Superfamily Member 13/genetics
KW - Up-Regulation
U2 - 10.1136/thoraxjnl-2012-202288
DO - 10.1136/thoraxjnl-2012-202288
M3 - Article
C2 - 23002173
SN - 0040-6376
VL - 68
SP - 76
EP - 81
JO - Thorax
JF - Thorax
IS - 1
ER -