Drosophila melanogaster – a suitable model system to study epithelial immune responses in-vivo

In the westernized countries, the number of inflammatory airway diseases caused by environmental factors (allergens, cigarette smoking, and air pollution) has steadily increased over the last decades. In this context, it has become obvious that the airway epithelium is not a mere target but plays an active role in the development, progression, and chronification of airway diseases. Due to the presence and tight interaction between airway epithelial cells, interstitial and smooth muscle cells as well as innate and adaptive immune cells in the airways, studies on airway epithelial immunity are merely impossible in vertebrate model organisms such as the mouse. In this context the fruit fly Drosophila melanogaster is suggested to be a highly attractive model, as the immune system of its airways is neither subject to the influence of adaptive immune cells nor do other immune cells (e.g. macrophages) migrate into the epithelium in response to an infection.

In Drosophila, the immune response of the airways relies exclusively on epithelial cells that are entirely immune-reactive. All of them are equipped with a variety of constitutively expressed soluble and membrane-bound pattern recognition receptors for pathogen recognition, scavenging and immune modulation. Whereas pathogen recognition is mediated by Nod and Toll-like receptors in men, Drosophila primarily detects and binds pathogen-associated molecular patterns (PAMPs) by so called gram-negative binding proteins (GNBPs) or peptidoglycan recognition proteins (PGRPs) such as e.g. PGRP-LE or -LC. The latter activate the TNF-α homologous signaling pathway Immune deficiency (Imd) which triggers exclusively the production and secretion of antimicrobial peptides within these cells in order to kill intruding pathogens. Similar to inflammatory reactions in bronchial and alveolar epithelial cells in men, JAK/STAT- (Janus kinase/Signal Transducer and Activator of Transcription) and Jun- (c-Jun N-terminal kinases) signaling also mediate immune reactions in the fly's airway epithelial cells in the course of an infection. Since the flies' innate immune system shares striking similarities with the human one at least at the level of molecular and genetic pathways, the fruit fly with its simplicity, its ease of genetic manipulations and its low genetic redundancy provides an excellent in-vivo model for biomedical research on human disease-related innate immune responses.