Toll-like Receptor 7-triggered Immune Response in the Lung Mediates Acute and Long-Lasting Suppression of Experimental Asthma

Rationale: Toll-like receptor (TLR) 7/8 ligands are promising candidate drugs for the treatment of allergic asthma and rhinitis. Although their clinical application depends on the development of strategies for topical administration to the lung, this has not been explored in preclinical disease models.Objectives: To examine the therapeutic effectiveness, persistence of effect, and mode of action of intranasal TLR7 ligand administration in allergic airway disease.Methods: Wild-type, IFN-α receptor (IFN-αR)−/−, IFN-γ−/−, CD8−/−, TLR7−/−, and radiation-induced chimeric mice deficient in hematopoietic TLR7 expression were subjected to an established model of allergic airway disease. R-848, a specific TLR7 agonist in mice, was administered prophylactically or therapeutically and effects of treatment on helper T-cell type 2 (Th2) responses, eosinophilia, goblet cell metaplasia, and airway hyperresponsiveness were assessed.Measurements and Main Results: Intranasal R-848 administration induced a transient immune ...