A Drosophila Asthma Model – What the Fly Tells Us About Inflammatory Diseases of the Lung

Abstract

Asthma and COPD are the most relevant inflammatory diseases of the airways. In western countries they show a steeply increasing prevalence, making them to a severe burden for health systems around the world. Although these diseases are typically complex ones, they have an important genetic component. Genome-wide association studies have provided us with a relatively small but comprehensive list of asthma susceptibility genes that will be extended and presumably completed in the near future. To identify the role of these genes in the physiology and pathophysiology of the lung, genetically tractable model organisms are indispensable and murine models were the only ones that have been extensively used. An urgent demand for complementary models is present that provide specific advantages lacking in murine models, especially regarding speed and flexibility. Among the model organisms available, only the fruit fly Drosophila melanogaster shares a comparable organ composition and at least a lung equivalent. It has to be acknowledged that the fruit fly Drosophila has almost completely been ignored as a model organism for lung diseases, simply because it is devoid of lungs. Nevertheless, its airway system shows striking similarities with the one of mammals regarding its physiology and reaction towards pathogens, which holds the potential to function as a versatile model in asthma-related diseases.

Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients

“…The high costs of transgenic and gene-deletion mouse models has restricted progress in this area. Thus it would be timely to investigate the potential of nonmammalian models, such as Drosophila species or zebrafish, as tools to investigate gene function because the genetic tractability and low cost of rearing these organisms are major advantages 201, 202. Better understanding of epithelial dysfunction and its interrelationship with airways inflammation and structural remodeling should help to define specific epithelial endotypes in asthmatic patients.…”

Transcriptional Regionalization of the Fruit Fly’s Airway Epithelium

“…These commonalities have been reported for diverse functional modules such as the epithelial innate immune system or the liquid clearance [7], [9]. It turned out that these similarities are unexpectedly far-reaching, which enabled the development of Drosophila models for inflammatory diseases of the lung, such as asthma [10]–[12]. Although much simpler organized and seemingly with a more homogenous structure throughout the entire organ, special cell types have been identified in the Drosophila airways.…”

Barriers to new drug development in respiratory disease

“…However, numerous biological processes and genes are conserved between these model systems and humans. These include asthma susceptibility genes involved in innate immunity [32,33], making these model systems attractive options for studying innate immune responses in isolation of an adaptive immune system. The genetic tractability of these organisms, together with the rapidly increasing number of transgenesis tools available, make them ideal models for understanding the role of individual genes, or gene clusters in a disease pathway, identifying putative candidate genes for further downstream functional analysis in other model systems.…”