Abstract
Allergic asthma is associated with exposure to allergens and non-allergenic bacterial products residing in common house dust, suggesting that bacterial products can act as adjuvants to promote allergic sensitization to innocuous inhaled antigens. We therefore tested the ability of various microbial products, signaling through different toll like receptors (TLR), to prime allergic sensitization to inhaled antigens. Of the products tested, bacterial flagellin primed the strongest Th2 and Th17 responses to co-instilled ovalbumin (OVA). Following subsequent challenge with aerosolized OVA, these mice displayed strong asthma-like responses, including airway eosinophilia, mucus cell hyperplasia and airway hyperresponsiveness. As with purified flagellin, instillation of HDE into the airways of mice also primed Th2 and Th17 immune responses to OVA, and following OVA challenge, the animals developed strong asthma-like responses. Repeated instillations of HDE without OVA also induced asthma-like responses, indicating that house dust contains both adjuvants and allergens. The adjuvant activity in HDE was not dependent on TLR4, which senses lipopolysaccharide (LPS), but was dependent on TLR5, which senses bacterial flagellin. These findings might be relevant to human asthma because human sera from asthmatics had higher levels of anti-flagellin antibodies than did sera from control individuals. Taken together, these findings suggest that bacterial flagellin, and not LPS, is the major adjuvant in common house dust and that flagellin promotes allergic asthma by priming allergic responses to otherwise innocuous inhaled antigens.
- © 2011 ERS
