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

A. Al-Garawi, M. Husain, D. Ilieva, A. A. Humbles, R. Kolbeck, M. R. Stampfli, P. M. O'Byrne, A. J. Coyle, M. Jordana

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13 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)832-843
Number of pages12
JournalThe Journal of Immunology
Volume188
Issue number2
DOIs
StatePublished - Dec 14 2011
Externally publishedYes

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