TLR ligands alter the phenotype of experimental acute allergic asthma in mice

Introduction: Clinical observations revealed that recurrent asthma exacerbations triggered by viral or bacterial infections are major risk factors for asthma aggravation towards a severe phenotype. Although the pathogenetic mechanisms underlying the development of severe asthma remain incompletely understood, recent observations strongly suggest a distinct pathobiology that is not merely an aggravation of the processes responsible for mild-to-moderate asthma. Interleukin-17 (IL-17) producing cells might be involved in these mechanisms ultimately leading to aggravation towards a severe phenotype. The present study aims to investigate, whether T-helper (Th) 17 cells are implicated in TLR triggered exacerbation of experimental allergic asthma.

Methods: We evaluated the effect of the two different TLR ligands, poly(I:C) (binding TLR3) and ODN1668 (binding TLR9), on experimental allergic asthma. Therefore, mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol. TLR ligands were applied intra-nasally after OVA aerosol challenge to provoke exacerbation of the asthmatic phenotype. Lung function, lung histology, broncho alveolar lavage (BAL) cells, and BAL IL-17 were assessed.

Results: Exacerbation of experimental allergic asthma could be triggered by both, local application of poly(I:C) as well as of ODN1668, as indicated by additional influx of neutrophils in to airway tissue and the broncho alveolar lumen together with a decline in lung function. However, IL-17 protein levels in BAL fluids were only marginally increased.

Discussion: These results demonstrate that TLR ligands aggravate the Th2 phenotype of experimental asthma. However, we could not detect large amounts of IL-17 indicating a minor role of it in these settings. In order to further exclude the implication of IL-17 in a future experiment we will perform the acute allergic asthma model in IL-17 deficient mice.