The role of airborne bacterial particulate in the development of allergic asthma

Allergic asthma is a chronic inflammatory disorder of the airways characterized by a biased polarization toward T helper 2 (Th2) adaptive immune responses to commonly inhaled antigens. Current studies are focusing on the involvement of particulate matter (PM) in the development of allergic asthma. It has been speculated that PM acts as an adjuvant by enhancing immune responses towards common environmental allergens. Bacterial components that are commonly found in PM fractions have been shown to play an important role in PM toxicity in in-vitro studies. Activation of Toll-like receptors (TLRs), which are involved in the recognition of microbial components by the innate immune system, leads to the production of molecules and cytokines essential for the induction of adaptive immunity. The hypothesis of this dissertation is that inhalation of bacterial cell wall components, mainly endotoxin, present as components of ambient PM will induce innate immune responses that promote the development of pulmonary allergic reactions through the activation of the TLR signaling cascade. To determine the prevalence and composition of airborne bacterial components in ambient PM, the levels of culturable bacteria and endotoxin were measured for a year. The concentrations of bacteria ranged from 50 to 1400 CFU/m3 with the highest concentrations during the Fall and Spring seasons. Bacteria associated with particles of 8mum or less in diameter were statistically correlated with the levels of PM10 and 85% of the bacteria stained Gram-positive. The average concentration of endotoxin present in ambient PM was 0.77 EU/m3 and had a mass median aerodynamic diameter of 3.5mum. Mice sensitized to ovalbumin with concentrated ambient particles (CAPS) as adjuvant developed an asthmatic phenotype characterized by increased levels of eosinophils, IL-5 and IgG1. Endotoxin levels were significantly higher in animals exposed to CAPS and TLR2 expression was elevated as well. To examine whether alveolar macrophages (AM) responses to CAPS were associated with the presence of endotoxin, in-vitro studies were performed using endotoxin inhibitors. Endotoxin was associated with the induction of IL-6 and nitric oxide. The production of IL-6 by AM might enhance the development of allergic responses in the airways by promoting the proliferation of Th2 lymphocytes.