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J Allergy Clin Immunol. 2012 Nov;130(5):1187-1196.e5. doi: 10.1016/j.jaci.2012.07.031. Epub 2012 Sep 13.

Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection.

Author information

1
Immunology Program, Benaroya Research Institute, Seattle, WA, USA.

Abstract

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.

PMID:
22981788
PMCID:
PMC4284103
DOI:
10.1016/j.jaci.2012.07.031
[Indexed for MEDLINE]
Free PMC Article

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