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

Handle URI:
http://hdl.handle.net/10754/599359
Title:
Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights
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.
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.
Publisher:
The American Association of Immunologists
Journal:
The Journal of Immunology
Issue Date:
14-Dec-2011
DOI:
10.4049/jimmunol.1102349
PubMed ID:
22174454
Type:
Article
ISSN:
0022-1767; 1550-6606
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.
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Full metadata record

DC FieldValue Language
dc.contributor.authorAl-Garawi, A.en
dc.contributor.authorHusain, M.en
dc.contributor.authorIlieva, D.en
dc.contributor.authorHumbles, A. A.en
dc.contributor.authorKolbeck, R.en
dc.contributor.authorStampfli, M. R.en
dc.contributor.authorO'Byrne, P. M.en
dc.contributor.authorCoyle, A. J.en
dc.contributor.authorJordana, M.en
dc.date.accessioned2016-02-28T06:05:30Zen
dc.date.available2016-02-28T06:05:30Zen
dc.date.issued2011-12-14en
dc.identifier.citationAl-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.en
dc.identifier.issn0022-1767en
dc.identifier.issn1550-6606en
dc.identifier.pmid22174454en
dc.identifier.doi10.4049/jimmunol.1102349en
dc.identifier.urihttp://hdl.handle.net/10754/599359en
dc.description.abstractRespiratory 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.en
dc.description.sponsorshipThis 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.en
dc.publisherThe American Association of Immunologistsen
dc.titleShifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insightsen
dc.typeArticleen
dc.identifier.journalThe Journal of Immunologyen
dc.contributor.institutionMcMaster University, Hamilton, Canadaen
dc.contributor.institutionMedImmune LLC, Gaithersburg, United Statesen
dc.contributor.institutionPfizer, New York, United Statesen

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