BACKGROUND: Respiratory viral infection, including respiratory syncytial virus (RSV) and rhinovirus, has been linked to respiratory disease in pediatric patients, including severe acute bronchiolitis and asthma exacerbation. OBJECTIVE: The study examined the role of the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) in the response to RSV infection. METHODS: Infection of human airway epithelial cells was used to examine TSLP induction after RSV infection. Air-liquid interface cultures from healthy children and children with asthma were also tested for TSLP production after infection. Finally, a mouse model was used to directly test the role of TSLP signaling in the response to RSV infection. RESULTS: Infection of airway epithelial cells with RSV led to the production of TSLP via activation of an innate signaling pathway that involved retinoic acid induced gene I, interferon promoter-stimulating factor 1, and nuclear factor-κB. Consistent with this observation, airway epithelial cells from asthmatic children a produced significantly greater levels of TSLP after RSV infection than cells from healthy children. In mouse models, RSV-induced TSLP expression was found to be critical for the development of immunopathology. CONCLUSION: These findings suggest that RSV can use an innate antiviral signaling pathway to drive a potentially nonproductive immune response and has important implications for the role of TSLP in viral immune responses in general.
BACKGROUND:Respiratory viral infection, including respiratory syncytial virus (RSV) and rhinovirus, has been linked to respiratory disease in pediatric patients, including severe acute bronchiolitis and asthma exacerbation. OBJECTIVE: The study examined the role of the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) in the response to RSV infection. METHODS: Infection of human airway epithelial cells was used to examine TSLP induction after RSV infection. Air-liquid interface cultures from healthy children and children with asthma were also tested for TSLP production after infection. Finally, a mouse model was used to directly test the role of TSLP signaling in the response to RSV infection. RESULTS: Infection of airway epithelial cells with RSV led to the production of TSLP via activation of an innate signaling pathway that involved retinoic acid induced gene I, interferon promoter-stimulating factor 1, and nuclear factor-κB. Consistent with this observation, airway epithelial cells from asthmatic children a produced significantly greater levels of TSLP after RSV infection than cells from healthy children. In mouse models, RSV-induced TSLPexpression was found to be critical for the development of immunopathology. CONCLUSION: These findings suggest that RSV can use an innate antiviral signaling pathway to drive a potentially nonproductive immune response and has important implications for the role of TSLP in viral immune responses in general.
Authors: Aarti Shikotra; David F Choy; Chandra M Ohri; Emma Doran; Claire Butler; Beverley Hargadon; Maria Shelley; Alexander R Abbas; Cary D Austin; Janet Jackman; Lawren C Wu; Liam G Heaney; Joseph R Arron; Peter Bradding Journal: J Allergy Clin Immunol Date: 2011-10-05 Impact factor: 10.793
Authors: Christopher L Grainge; Laurie C K Lau; Jonathon A Ward; Valdeep Dulay; Gemma Lahiff; Susan Wilson; Stephen Holgate; Donna E Davies; Peter H Howarth Journal: N Engl J Med Date: 2011-05-26 Impact factor: 91.245
Authors: Dennis M Lindell; Susan B Morris; Maria P White; Lara E Kallal; Phillip K Lundy; Tarek Hamouda; James R Baker; Nicholas W Lukacs Journal: PLoS One Date: 2011-07-15 Impact factor: 3.240
Authors: Bing Tian; Jun Yang; Yingxin Zhao; Teodora Ivanciuc; Hong Sun; Roberto P Garofalo; Allan R Brasier Journal: J Virol Date: 2017-02-28 Impact factor: 5.103