UC San Diego

Laboratory and epidemiological studies suggest that aside from allergens themselves, living environments are rich in their content of toll-like receptor ligands and other allergen nonspecific immunostimulatory molecules. In purified form, many of these molecules impact greatly on allergic disease outcome measures in animal models. However, the immunomodulatory influence of living environments on the pathophysiology of allergic asthma has yet to be directly assessed. Therefore, based on the premise that particulates with immunostimulatory activity collect in house dust, we investigated the bioactivities of sterile but unpurified house dust extracts (HDEs) in a murine asthma model. With intermittent airway delivery, HDEs were potent Th2 adjuvants that promoted development of aeroallergen hypersensitivities and experimental asthma. In contrast, mice treated by daily airway HDE delivery were rendered resistant to aeroallergen sensitization. In other experiments, previously Th2- sensitized mice received daily or intermittent airway HDE delivery during the allergen challenge period. Under these experimental circumstances, daily delivery was far more effective than intermittent delivery but both HDE delivery schedules led to attenuated Th2 hypersensitivity responses with increased airway neutrophil recruitment. A final series of experiments demonstrated that sensitized mice treated with daily but not intermittent HDE delivery during the primary airway allergen challenge period had persistently attenuated airway hypersensitivity responses when challenged with allergen alone, a month later. Considered together, these investigations provide direct evidence that airway exposures to the immunostimulatory constituents of living environments have the potential to either promote or prevent manifestations of allergic respiratory diseases, depending on exposure dose and frequency