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  • Title: Airway peptidoglycan and immunostimulatory DNA exposures have divergent effects on the development of airway allergen hypersensitivities.
    Author: Chisholm D, Libet L, Hayashi T, Horner AA.
    Journal: J Allergy Clin Immunol; 2004 Mar; 113(3):448-54. PubMed ID: 15007346.
    Abstract:
    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 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. 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.
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