TLR-3 triggered aggravation of experimental asthma depends on IL-17

Recent clinical studies revealed that recurrent viral and bacterial infections are major risk factors for the aggravation of allergic bronchial asthma. However, the underlying cellular mechanisms for this aggravation remain incompletely understood. Interleukin-17 (IL-17) producing cells might be involved in this process. The present study aims at investigating wether T-helper (Th) 17 cells are implicated in TLR triggered aggravation of experimental allergic asthma.

Therefore, mice were sensitized to ovalbumin (OVA) and subsequently challenged with OVA aerosol to provoke a local allergic inflammation of the airways. To test the hypothesis that TLR-3 stimulation provokes an aggravation of the asthmatic phenotype which depends on IL-17, Poly(I:C), a synthetic TLR-3 ligand, was applied intra-nasally 24 hours after OVA aerosol challenge both in wild type and in IL-17 deficient mice. Lung function, lung histology, broncho-alveolar lavage (BAL) cell counts, and IL-17 in BAL fluids were assessed and compared with control groups.

Local application of poly(I:C) caused aggravation of the acute experimental asthma phenotype in wild type mice. The aggravation was identified by impaired lung function and by profound infiltration of neutrophils into the airways as well as the broncho-alveolar lumen, which was nearly absent in the control group. However, IL-17 protein levels in BAL fluids were only marginally increased. The poly(I:C) triggered infiltration of neutrophils observed in wild type mice was absent in IL-17 deficient mice.

These data suggest that local application of the TLR-3 ligand poly(I:C) leads to an aggravation of the acute phenotype of experimental allergic asthma in mice, which depends on IL-17.