Toll-like receptor (TLR) mediated signaling induces pro-inflammatory responses and can both suppress and exacerbate allergic responses in the airways. The aim of our study was to directly compare the efficacy of different
TLR agonists in inhibiting or exacerbating the development of Th2-mediated responses in the airways and investigate if the suppressive effects were associated with increased pro-inflammatory responses. Mice were immunized on day 0, 14 and 21 by
intraperitoneal injection of
ovalbumin/alum and exposed to
ovalbumin aerosol on day 26 and 27. TLR2, TLR3, TLR4, TLR7 and TLR9 agonists (0.001, 0.01, 0.1, or 1 mg/kg) were administered intratracheally 1 h before each
allergen exposure. Both the TLR7 and TLR9 agonists dose dependently reduced airway
eosinophilia, while the TLR3 agonist only reduced airway
eosinophilia at a dose of 1.0 mg/kg. The TLR2 and TLR4 agonists potentiated
eosinophilia. All
TLR agonists enhanced neutrophil numbers at doses as low as 0.01 mg/kg, in particular TLR2 and TLR4 agonists. TLR7 and TLR9 agonists also significantly reduced
IL-4 and
IL-5 levels and all
TLR agonists, with the exception of TLR7, enhanced the amount IL-1β,
IL-6, and TNF-α detected in the whole lung lavage. Only application of TLR9 agonist induced detectable levels of
IL-10 in the lung. Suppressive effects of the
TLR agonists were not dependent upon IFN-γ and
IL-10 or associated with increased numbers of Foxp3(+)CD4(+) Tr cells in the lavage fluid. Airway resistance was reduced significantly only when TLR7 agonist was administered. When applied therapeutically 2 days after
allergen exposure, all
TLR agonists, except TLR2, similarly reduced airway
eosinophilia and
IL-4 levels. Taken together our results show that TLR7 agonists had the strongest
anti-asthmatic effects with the lowest pro-inflammatory potential, suggesting that activating TLR7 may have the greatest potential to treat allergic disorders in humans.