Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

<p>Abstract</p> <p>Background</p> <p>Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV), increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a spe...

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Main Authors: Asquith Kelly L, Domachowske Joseph B, Rosenberg Helene F, Herbert Cristan, Hansbro Nicole, Siegle Jessica S, Foster Paul S, Kumar Rakesh K
Format: Article
Language:English
Published: BMC 2010-02-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/11/1/14
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author Asquith Kelly L
Domachowske Joseph B
Rosenberg Helene F
Herbert Cristan
Hansbro Nicole
Siegle Jessica S
Foster Paul S
Kumar Rakesh K
author_facet Asquith Kelly L
Domachowske Joseph B
Rosenberg Helene F
Herbert Cristan
Hansbro Nicole
Siegle Jessica S
Foster Paul S
Kumar Rakesh K
author_sort Asquith Kelly L
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV), increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma.</p> <p>Methods</p> <p>We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants) and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR) and host immunological responses.</p> <p>Results</p> <p>Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG<sub>1 </sub>as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice that received chronic allergen challenge, regardless of neonatal PVM infection, and were not dependent on signalling via the IL-4 receptor.</p> <p>Conclusion</p> <p>In this mouse model, interaction between early-life viral infection and allergen sensitisation/challenge is essential for development of the characteristic features of childhood asthma, including allergic inflammation and a Th2-biased immune response.</p>
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spelling doaj.art-10eca9d871b84f92879c6738b8226f382022-12-21T22:40:19ZengBMCRespiratory Research1465-99212010-02-011111410.1186/1465-9921-11-14Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in miceAsquith Kelly LDomachowske Joseph BRosenberg Helene FHerbert CristanHansbro NicoleSiegle Jessica SFoster Paul SKumar Rakesh K<p>Abstract</p> <p>Background</p> <p>Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV), increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma.</p> <p>Methods</p> <p>We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants) and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR) and host immunological responses.</p> <p>Results</p> <p>Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG<sub>1 </sub>as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice that received chronic allergen challenge, regardless of neonatal PVM infection, and were not dependent on signalling via the IL-4 receptor.</p> <p>Conclusion</p> <p>In this mouse model, interaction between early-life viral infection and allergen sensitisation/challenge is essential for development of the characteristic features of childhood asthma, including allergic inflammation and a Th2-biased immune response.</p>http://respiratory-research.com/content/11/1/14
spellingShingle Asquith Kelly L
Domachowske Joseph B
Rosenberg Helene F
Herbert Cristan
Hansbro Nicole
Siegle Jessica S
Foster Paul S
Kumar Rakesh K
Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
Respiratory Research
title Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
title_full Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
title_fullStr Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
title_full_unstemmed Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
title_short Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
title_sort early life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice
url http://respiratory-research.com/content/11/1/14
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