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

A Al-Garawi, R Fattouh, F Botelho, T D Walker, S Goncharova, C-L Moore, M Mori, J S Erjefalt, D K Chu, A A Humbles, R Kolbeck, M R Stampfli, P M O'Byrne, A J Coyle, M Jordana

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25 Scopus citations


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 CD8α + 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.
Original languageEnglish (US)
Pages (from-to)682-694
Number of pages13
JournalMucosal Immunology
Issue number6
StatePublished - Aug 31 2011
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We gratefully acknowledge the technical help of Mary-Jo Smith, Mary Bruni, and Natalia Arias. We also thank Dr Jack Gauldie for careful review of the manuscript and Marie Colbert for administrative assistance. This research was partially funded by the Canadian Institute of Health Research (CIHR) and MedImmune LLC. AA-G. holds a Scholar Award from King Abdullah University of Science and Technology; RF holds an Ontario Graduate Fellowship; MJ holds a Senior Canada Research Chair in Immunobiology of Respiratory Disease and Allergy.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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