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    Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

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    Type
    Article
    Authors
    Al-Garawi, A.
    Husain, M.
    Ilieva, D.
    Humbles, A. A.
    Kolbeck, R.
    Stampfli, M. R.
    O'Byrne, P. M.
    Coyle, A. J.
    Jordana, M.
    Date
    2011-12-14
    Online Publication Date
    2011-12-14
    Print Publication Date
    2012-01-15
    Permanent link to this record
    http://hdl.handle.net/10754/599359
    
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    Abstract
    Respiratory viral infections have been associated with an increased incidence of allergic asthma. However, the mechanisms by which respiratory infections facilitate allergic airway disease are incompletely understood.We previously showed that exposure to a low dose of house dust mite (HDM) resulted in enhanced HDM-mediated allergic airway inflammation, and, importantly, marked airway hyperreactivity only when allergen exposure occurred during an acute influenza A infection. In this study, we evaluated the impact of concurrent influenza infection and allergen exposure at the genomic level, using whole-genome micro-array. Our data showed that, in contrast to exposure to a low dose of HDM, influenza A infection led to a dramatic increase in gene expression, particularly of TLRs, C-type lectin receptors, several complement components, as well as FcεR1. Additionally, we observed increased expression of a number of genes encoding chemokines and cytokines associated with the recruitment of proinflammatory cells. Moreover, HDM exposure in the context of an influenza A infection resulted in the induction of unique genes, including calgranulin A (S100a8), an endogenous damage-associated molecular pattern and TLR4 agonist. In addition, we observed significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype. Copyright © 2012 by The American Association of Immunologists, Inc.
    Citation
    Al-Garawi A, Husain M, Ilieva D, Humbles AA, Kolbeck R, et al. (2011) Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights. The Journal of Immunology 188: 832–843. Available: http://dx.doi.org/10.4049/jimmunol.1102349.
    Sponsors
    This work was supported in part by the Canadian Institute of Health Research andMedImmune LLC. A.A.-G. holds a scholar award from the King Abdullah Universityof Science and Technology, and M.J. holds a Senior Canada Research Chair inImmunobiology of Respiratory Disease and Allergy.
    Publisher
    The American Association of Immunologists
    Journal
    The Journal of Immunology
    DOI
    10.4049/jimmunol.1102349
    PubMed ID
    22174454
    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.1102349
    Scopus Count
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