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 microarray. 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.