Mechanisms of allergy and clinical immunologyThymic stromal lymphopoietin is induced by respiratory syncytial virus–infected airway epithelial cells and promotes a type 2 response to infection
Section snippets
Cells and virus
Normal human BECs (NHBECs) were maintained in appropriate medium according to the manufacturer's instruction (Lonza, Walkersville, Md). The human lung epithelial cell line A549 was maintained in Dulbecco modified Eagle medium (DMEM) with 10% FBS and antibiotics. Murine air-liquid interface (ALI) cultures were grown from mouse tracheal epithelial cells and differentiated as described.13 Generation of RIG-I knockout (KO) and IFN-α receptor KO mouse embryonic fibroblasts (MEFs) was previously
Induction of human TSLP expression by RSV infection of primary AECs
Severe infection with the family Paramyxoviridae virus during childhood was found to strongly correlate with subsequent asthma development, and infection in adults with asthma commonly led to significant bouts of exacerbated disease. Further, a significant body of work has now reported the critical nature of TSLP expression by AECs in promoting the asthma phenotype.5, 7 In addition, several studies have now reported that infection of AECs with a variety of viruses or treatment with the viral
Discussion
The important role of respiratory virus infection on the onset of asthma, as well as the exacerbation of disease in patients with established asthma, has become clear.36, 37, 38 However, the mechanism responsible for these effects has remained unclear. In this study, we report that infection of airway epithelium with Paramyxoviridae family viruses induces robust expression of TSLP, a TH2-promoting cytokine. This finding is particularly interesting given that RSV infection in young children has
References (57)
- et al.
Host immunity during RSV pathogenesis
Int Immunopharmacol
(2008) - et al.
Respiratory virus-induced regulation of asthma-like responses in mice depends upon CD8 T cells and interferon-g production
Am J Path
(2007) - et al.
Differential immune responses and pulmonary pathophysiology are induced by two different strains of respiratory syncytial virus
Am J Pathol
(2006) - et al.
Function of RIG-I-like receptors in antiviral innate immunity
J Biol Chem
(2007) - et al.
CARD games between virus and host get a new player
Trends Immunol
(2006) - et al.
Recognition of viruses by cytoplasmic sensors
Curr Opin Immunol
(2010) - et al.
Respiratory syncytial virus and other respiratory viruses during the first 3 months of like promote a local Th2-like response
J Allergy Clin Immunol
(2005) - et al.
Pathogenesis of respiratory syncytial virus bronchiolitis-related wheezing
Paediatr Respir Rev
(2004) The epithelium takes centre stage in asthma and atopic dermatitis
Trends Immunol
(2007)- et al.
Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity
Curr Opin Immunol
(2007)
Epithelial dysfunction in asthma
J Allergy Clin Immunol
Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life
Thorax
Community study of role of viral infections in exacerbations of asthma in 9-11 year old children
BMJ
Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms
J Immunol
Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity
J Immunol
TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses
J Immunol
Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice
Nat Immunol
A role for TSLP in the development of inflammation in an asthma model
J Exp Med
TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand
J Exp Med
TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells
J Immunol
Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP
Nat Immunol
Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses
J Immunol
Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa
Infect Immun
Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence
J Virol
Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity
J Virol
Respiratory syncytial virus-induced chemokine production: linking viral replication to chemokine production in vitro and in vivo
J Infect Dis
The use of non-bronchoscopic brushings to study the paediatric airway
Respir Res
Cutting edge: Inhibition of NF-kappaB-mediated TSLP expression by retinoid X receptor
Cutting Edge J Immunol
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Supported by the National Institutes of Health (grants AI068731, HL098067, AR055695, and AR056113 to S.F.Z.; grant HL102708 to S.F.Z. and J.S.D.; grants AI060389 and AI083019 to M.G. Jr; and grant HL059178 to N.W.L.).
Disclosure of potential conflict of interest: M. Headley, M. Gale, J. S. Debley, and N. W. Lukacs have received research support from the National Institutes of Health (NIH). S. F. Ziegler has received research support from the NIH, has received lecture fees from the American Academy of Allergy, Asthma & Immunology, and has received travel expenses from the Federation of Clinical Immunology Services. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.