Airway peptidoglycan and immunostimulatory DNA exposures have divergent effects on the development of airway allergen hypersensitivities

Background Environmental exposures to toll-like receptor (TLR) ligands have been suggested to provide immunologic protection against allergic diseases. However, some TLRs use unique intracellular signaling pathways, suggesting that ambient TLR ligand exposures might induce a range of host responses. Objective These investigations compared peptidoglycan (PGN; TLR2)–induced and immunostimulatory sequence DNA oligodeoxynucleotide (ISS-ODN; TLR9)–induced innate responses and determined how airway exposures to these TLR ligands affect adaptive immunity and the asthmatic phenotype. Methods In in vitro and in vivo studies innate responses to PGN and ISS-ODN were compared. Alternatively, mice were intranasally immunized with ovalbumin (OVA) alone or OVA plus PGN or ISS-ODN, and adaptive immune profiles and responses to airway OVA challenge were assessed. Results PGN and ISS-ODN induced divergent innate responses predictive of their having T H 2- and T H 1-biasing adjuvant potential, respectively. Consistent with these findings, mice intranasally immunized with OVA alone had relatively weak adaptive responses, whereas intranasal OVA/PGN– and OVA/ISS-ODN–coimmunized mice had much stronger humoral and cellular responses that were T H 2 and T H 1 biased, respectively. Finally, on airway allergen challenge, mice intranasally immunized with OVA alone had modest T H 2-biased airway hypersensitivity responses, whereas airway responses were greatly exaggerated for intranasal OVA/PGN–immunized mice. In contrast, intranasal OVA/ISS-ODN–immunized mice had little evidence of airway hypersensitivity after airway allergen challenge. Conclusions Considered in a larger context, these results suggest that inspired air is likely to contain TLR ligands capable of both preventing and precipitating the asthmatic phenotype.