Advanced

Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood

Al-Garawi, A.; Fattouh, R.; Botelho, F.; Walker, T. D.; Goncharova, S.; Moore, C-L; Mori, Michiko LU ; Erjefält, Jonas LU ; Chu, D. K. and Humbles, A. A., et al. (2011) In Mucosal Immunology 4(6). p.682-694
Abstract
The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in life. Neonatal (8-day-old) mice were infected with influenza virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice exposed to HDM exhibited negligible immune responsiveness to HDM, but not to influenza A. HDM responsiveness in adults was associated with distinct Ly6c(+) CD11b(+) inflammatory dendritic cell and CD8... (More)
The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in life. Neonatal (8-day-old) mice were infected with influenza virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice exposed to HDM exhibited negligible immune responsiveness to HDM, but not to influenza A. HDM responsiveness in adults was associated with distinct Ly6c(+) CD11b(+) inflammatory dendritic cell and CD8 alpha(+) plasmacytoid (pDC) populations that were absent in HDM-exposed infant mice, suggesting an important role in HDM-mediated inflammation. Remarkably, HDM hyporesponsiveness was overcome when exposure occurred concurrently with an acute influenza infection; young mice now displayed robust allergen-specific immunity, allergic inflammation, and lung remodeling. Remodeling persisted into early adulthood, even after prolonged discontinuation of allergen exposure and was associated with marked impairment of lung function. Our data demonstrate that allergen exposure coincident with acute viral infection in early life subverts constitutive allergen hyporesponsiveness and imprints an asthmatic phenotype in adulthood. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
4
issue
6
pages
682 - 694
publisher
Nature Publishing Group
external identifiers
  • wos:000296429200012
  • scopus:80054959872
ISSN
1933-0219
DOI
10.1038/mi.2011.35
language
English
LU publication?
yes
id
eaacff9b-1555-4cc9-a9f5-6979dfd81bb9 (old id 2207753)
date added to LUP
2011-11-30 09:12:59
date last changed
2017-01-01 03:29:46
@article{eaacff9b-1555-4cc9-a9f5-6979dfd81bb9,
  abstract     = {The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in life. Neonatal (8-day-old) mice were infected with influenza virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice exposed to HDM exhibited negligible immune responsiveness to HDM, but not to influenza A. HDM responsiveness in adults was associated with distinct Ly6c(+) CD11b(+) inflammatory dendritic cell and CD8 alpha(+) plasmacytoid (pDC) populations that were absent in HDM-exposed infant mice, suggesting an important role in HDM-mediated inflammation. Remarkably, HDM hyporesponsiveness was overcome when exposure occurred concurrently with an acute influenza infection; young mice now displayed robust allergen-specific immunity, allergic inflammation, and lung remodeling. Remodeling persisted into early adulthood, even after prolonged discontinuation of allergen exposure and was associated with marked impairment of lung function. Our data demonstrate that allergen exposure coincident with acute viral infection in early life subverts constitutive allergen hyporesponsiveness and imprints an asthmatic phenotype in adulthood.},
  author       = {Al-Garawi, A. and Fattouh, R. and Botelho, F. and Walker, T. D. and Goncharova, S. and Moore, C-L and Mori, Michiko and Erjefält, Jonas and Chu, D. K. and Humbles, A. A. and Kolbeck, R. and Stampfli, M. R. and O'Byrne, P. M. and Coyle, A. J. and Jordana, M.},
  issn         = {1933-0219},
  language     = {eng},
  number       = {6},
  pages        = {682--694},
  publisher    = {Nature Publishing Group},
  series       = {Mucosal Immunology},
  title        = {Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood},
  url          = {http://dx.doi.org/10.1038/mi.2011.35},
  volume       = {4},
  year         = {2011},
}