Age difference in the immune response to endotoxin (LPS) shapes Th2-mediated airway inflammation and development of asthma.

Abstract

Abstract In addition to genetic factors, environmental exposures is also of primary importance for the development of asthma/allergy disorders in children, as demonstrated by epidemiological data showing children growing up in traditional farms seem to develop asthma less often than children growing up in urban areas. According to the hygiene hypothesis, this is due to increased exposure to endotoxin (LPS) and other farm-related microorganism-derived compounds. However little is known about how early-life contact to microbial compounds influence the development of asthma. Here we show that house dust mite (HDM) allergen sensitization in adult mice (8 weeks-old) induced T-helper type 2 (Th2)- driven airway inflammation, i.e., influx of activated Th2 cells into the airways, airway eosinophilic inflammation and increased IgE-producing plasmablasts. In contrast, HDM allergen sensitization with low-dose LPS (10 μg) abrogated HDM-driven Th2-mediated allergic airway inflammation without increasing antigen-specific Th1 cell trafficking into the airways. Importantly, unlike adults, infant mice (3 weeks-old) exposed to HDM with low-dose LPS (10 μg) developed Th2 responses allergic airway inflammation and required allergen sensitization with high-dose LPS (100 μg) to effectively suppress allergen-specific Th2 responses and allergic inflammation. These results show that airway exposure levels of endotoxin provide different protection against asthma and allergies in adults and infants and suggest that Infants are more vulnerable to prime type 2 cell dominant responses to inhaled allergens in the presence of low dose endotoxin, which will shape future effector Th2 responses and Th2-mediated airway inflammation throughout adult life.