TLR9-based immunotherapy for allergic disease.

A significant amount of data generated over the last few years supports the contention that Toll-like receptor (TLR) 9-based immunotherapy is effective in the prevention and treatment of animal models of allergic disorders. We will review here our experience with two distinct therapeutic strategies: TLR9-based immunomodulation and TLR9-based vaccination. Immunomodulation of allergic inflammation by TLR9 ligand (TLR9-L) is transient. It prevents both the early and late phases of the allergic reaction in experimental models of allergic asthma, rhinitis, and conjunctivitis. It also reverses ongoing allergic inflammation. Indoleamine 2.3-dioxygenase, the rate-limiting enzyme of tryptophan, is induced by TLR9-L and mediates, in part, these anti-inflammatory effects. TLR9-based immunomodulation is independent of allergens and, therefore, has a potential therapeutic advantage in a broad spectrum of allergic patients. On the other hand, TLR9-based vaccination therapy is an allergen-specific mode of immunotherapy, which provides long-term inhibition of allergen-specific hypersensitivities. Current clinical trials with TLR9-based immunotherapy demonstrate high immunogenic and therapeutic efficacy, as well as improved safety when compared with conventional allergen desensitization. Thus, if proven efficient, therapeutic strategies with TLR9-L may revolutionize the current treatment of allergic diseases.