Farming exposure and asthma phenotypes

The aim of this thesis was to assess the mechanisms underlying paradoxical effects of farm exposure, i.e. protection against allergic disorders and inducing non-allergic lung disease. To study allergic asthma, house dust mite mouse (HDM) models of asthma were used, whereas non-allergic asthma was investigated in a mouse model of farm dust exposure and in occupationally exposed subjects.

We propose that macrophages play a role in both protecting and inducing consequences of farm dust exposures, since we showed that farm dust modulates macrophage activation, inducing a phenotype that is related to non-allergic lung disease and blocking the differentiation of a macrophage phenotype that is related to allergic inflammation. Furthermore, we show that Fluticasone propionate treatment reduced airway hyper-responsiveness in mice with non-allergic lung disease while it did not affect lung neutrophilia. In conclusion, we have shown that exposures to farm dust extracts in mice and occupational exposure to farm environment induce a shift in the immune system towards Th1 and Th17 cells and MHC class IIhigh IRF5+ macrophages (or M1 macrophages). This shift may protect against Th2-related disorders, such as allergic asthma, but is associated with risk to develop non-allergic asthma. Furthermore, we propose that IL-1β and IL-17 can play an important role in the development and severity of non-allergic airway hyper-responsiveness.

Dissertation: http://hdl.handle.net/11370/3faf05fb-ff01-4658-a2d2-f7e65e4ed37d