• Dugald Chisholm, Lev Libet, Tomoko Hayashi, and Anthony A Horner.
• Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0663, USA.
• J. Allergy Clin. Immunol. 2004 Mar 1; 113 (3): 448-54.

BackgroundEnvironmental 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.ObjectiveThese 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.MethodsIn 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.ResultsPGN and ISS-ODN induced divergent innate responses predictive of their having TH2- and TH1-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 TH2 and TH1 biased, respectively. Finally, on airway allergen challenge, mice intranasally immunized with OVA alone had modest TH2-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.ConclusionsConsidered 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.

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