Abstract
Asthma is a chronic inflammatory disease that is characterised by airway narrowing due to inflammation and remodeling. This pathology makes airways hyperresponsive to a variety of environmental factors allergens, viruses, among others. Our group has studied the role of the alveolar macrophages (AMs) from asthmatics in response to respiratory viruses, mainly rhinovirus (RV), which have shown a reduction in RV-induced interferons (INFs) in severe asthmatics compared to healthy. Airways epithelium also plays an active role in immunity and inflammation and has been shown to be impaired in asthmatics, being it more permeable to environmental factors and overexpresses proinflammatory cytokines. Part of our team (Grainge et al., N Engl J Med 2011;364:2006-15) showed how bronchoconstriction affects epithelium remodeling stimulating collagen synthesis and an increase in the number of glandular cells. Numerous environmental factors interact to influence susceptibility and trigger bronchoconstriction. Our goal is to evaluate the effect of bronchoconstriction on the immune system, macrophages and epithelial cells, on their transcriptome (through RNA-sequencing) and on their response to virus. We have recruited 24 mild asthmatics that underwent methacholine challenge (bronchoconstriction) or saline challenge (control group, no bronchoconstriction). Our preliminary data show significant differences in the immune response after the asthma attack, with macrophages expressing more inflammatory cytokines after bronchoconstriction than before, when exposed to RV. These results suggest that macrophages may become more pro-inflammatory during and after bronchoconstriction, thus enhancing inflammation in the lungs.
- Copyright ©the authors 2016