Airway remodeling: The Drosophila model permits a purely epithelial perspective

Abstract

Airway remodeling is an umbrella term for structural changes in the conducting airways that occur in chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). The pathobiology of remodeling involves multiple mesenchymal and lymphoid cell types and finally leads to a variety of hardly reversible changes such as hyperplasia of goblet cells, thickening of the reticular basement membrane, deposition of collagen, peribronchial fibrosis, angiogenesis and hyperplasia of bronchial smooth muscle cells. In order to develop solutions for prevention or innovative therapies, these complex processes must be understood in detail which requires their deconstruction into individual building blocks. In the present manuscript we therefore focus on the role of the airway epithelium and introduce Drosophila melanogaster as a model. The simple architecture of the flies' airways as well as the lack of adaptive immunity allows to focus exclusively on the importance of the epithelium for the remodeling processes. We will review and discuss genetic and environmentally induced changes in epithelial structures and molecular responses and propose an integrated framework of research for the future.

Bacteria and viruses and their role in the preschool wheeze to asthma transition

“…[83][84][85] From another perspective, the duration of airway hyperresponsiveness (AHR), as a marker of altered airway wall response and an indirect marker of asthma severity, is significantly prolonged in atopic asthmatic school aged children, potentially increasing the likelihood of asthma persistence and/or the transition from "recurrent wheeze" to "persistent asthma". 63 Airway wall changes induced by viral infections accelerate AHR, as indicated by the "Drosophila model" which permits a purely epithelial perspective, 86 either via mechanical pathways, that is, altered airway dimensions resulting in enhanced airway narrowing or through the physiological loss of the airway stabilizing effect, 87 although a clear correlation between thickened airway membrane and AHR could not be confirmed in other cohort studies. 88 These data indicate that viral, and particularly RV, infections may enhance airway remodeling and a more stable asthmatic phenotype, more so in atopic individuals.…”

Animals in Respiratory Research

“…The fruit fly has only one innate immune system but can use two pathogen recognition pathways: the Toll-like receptor and the immune deficiency (IMD) pathway [ 207 ]. In the tracheal epithelium, only the IMD pathway is active, and antimicrobial peptides are secreted when pathogens penetrate the epithelial barrier.…”

Experimental Animal Models in Respiratory Diseases

“…The respiratory organ of the fruit fly D. melanogaster is the tracheal system, a network of epithelial tubes that branch throughout the body, carrying gases to tissues and organs. This network takes in gases from respiratory openings called spiracles, which provide an external connection to the system, and transports them to tissues and organs through tracheal branches that branch out in the body (8).…”