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

  • Thomas Roeder
  • Kerstin Isermann
  • Kim Kallsen
  • Karin Uliczka
  • Christina Wagner
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 710)


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.


Innate Immune System Adaptive Immunity Airway Epithelial Cell Airway Epithelium Drosophila Model 



Research in our group was sponsored by the German Research Foundation (DFG) as parts of the SFB Transregio-22 (Teilprojekt A7) and the Cluster Inflammation@interfaces.


  1. Affolter M, Bellusci S, Itoh N, Shilo B, Thiery JP, Werb Z (2003) Tube or not tube: remodeling epithelial tissues by branching morphogenesis. Dev Cell 4(1):11–18PubMedCrossRefGoogle Scholar
  2. Arbouzova NI, Zeidler MP (2006) JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development 133(14):2605–2616PubMedCrossRefGoogle Scholar
  3. Baker KD, Thummel CS (2007) Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila. Cell Metab 6(4):257–266PubMedCrossRefGoogle Scholar
  4. Bellen HJ, Levis RW, Liao G, He Y, Carlson JW, Tsang G, Evans-Holm M, Hiesinger PR, Schulze KL, Rubin GM, Hoskins RA, Spradling AC (2004) The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167(2):761–781PubMedCrossRefGoogle Scholar
  5. Bier E (2005) Drosophila, the golden bug, emerges as a tool for human genetics. Nat Rev Genet 6(1):9–23PubMedCrossRefGoogle Scholar
  6. Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118(2):401–415PubMedGoogle Scholar
  7. Broide DH, Lawrence T, Doherty T, Cho JY, Miller M, McElwain K, McElwain S, Karin M (2005) Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in airway epithelium. Proc Natl Acad Sci USA 102(49):17723–17728PubMedCrossRefGoogle Scholar
  8. Chan HY, Bonini NM (2000) Drosophila models of human neurodegenerative disease. Cell Death Differ 7(11):1075–1080PubMedCrossRefGoogle Scholar
  9. Chien S, Reiter LT, Bier E, Gribskov M (2002) Homophila: human disease gene cognates in Drosophila. Nucleic Acids Res 30(1):149–151PubMedCrossRefGoogle Scholar
  10. Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M, Gasser B, Kinsey K, Oppel S, Scheiblauer S, Couto A, Marra V, Keleman K, Dickson BJ (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448(7150):151–156PubMedCrossRefGoogle Scholar
  11. Feany MB, Bender WW (2000) A Drosophila model of Parkinson’s disease. Nature 404(6776):394–398PubMedCrossRefGoogle Scholar
  12. Finkelman FD, Wills-Karp M (2008) Usefulness and optimization of mouse models of allergic airway disease. J Allergy Clin Immunol 121(3):603–606PubMedCrossRefGoogle Scholar
  13. Fortini ME, Skupski MP, Boguski MS, Hariharan IK (2000) A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol 150(2):F23–F30PubMedCrossRefGoogle Scholar
  14. Ghabrial A, Luschnig S, Metzstein MM, Krasnow MA (2003) Branching morphogenesis of the Drosophila tracheal system. Annu Rev Cell Dev Biol 19:623–647PubMedCrossRefGoogle Scholar
  15. Goswami S, Angkasekwinai P, Shan M, Greenlee KJ, Barranco WT, Polikepahad S, Seryshev A, Song LZ, Redding D, Singh B, Sur S, Woodruff P, Dong C, Corry DB, Kheradmand F (2009) Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma. Nat Immunol 10(5):496–503PubMedCrossRefGoogle Scholar
  16. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN (2009) House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 15(4):410–416PubMedCrossRefGoogle Scholar
  17. Holgate ST (2007) The epithelium takes centre stage in asthma and atopic dermatitis. Trends Immunol 28(6):248–251PubMedCrossRefGoogle Scholar
  18. Holgate ST, Polosa R (2008) Treatment strategies for allergy and asthma. Nat Rev Immunol 8(3):218–230PubMedCrossRefGoogle Scholar
  19. Holloway JW, Yang IA, Holgate ST (2008) Interpatient variability in rates of asthma progression: can genetics provide an answer? J Allergy Clin Immunol 121(3):573–579PubMedCrossRefGoogle Scholar
  20. Lemaitre B, Hoffmann J (2007) The host defense of Drosophila melanogaster. Annu Rev Immunol 25:697–743PubMedCrossRefGoogle Scholar
  21. McGuire SE, Le PT, Osborn AJ, Matsumoto K, Davis RL (2003) Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302(5651):1765–1768PubMedCrossRefGoogle Scholar
  22. Page-McCaw A, Serano J, Sante JM, Rubin GM (2003) Drosophila matrix metalloproteinases are required for tissue remodeling, but not embryonic development. Dev Cell 4(1):95–106PubMedCrossRefGoogle Scholar
  23. Pantano C, Ather JL, Alcorn JF, Poynter ME, Brown AL, Guala AS, Beuschel SL, Allen GB, Whittaker LA, Bevelander M, Irvin CG, Janssen-Heininger YM (2008) Nuclear factor-kappaB activation in airway epithelium induces inflammation and hyperresponsiveness. Am J Respir Crit Care Med 177(9):959–969PubMedCrossRefGoogle Scholar
  24. Potter CJ, Tasic B, Russler EV, Liang L, Luo L (2010) The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell 141:536–548PubMedCrossRefGoogle Scholar
  25. Roeder T, Isermann K, Kabesch M (2009) Drosophila in asthma research. Am J Respir Crit Care Med 179(11):979–983PubMedCrossRefGoogle Scholar
  26. Ruehle H (1932) Das larvale Tracheensystem von Drosophila melanogaster Meigen und seine Variabilität. Z Wiss Zool 141:159–245Google Scholar
  27. Shuai K, Liu B (2003) Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3(11):900–911PubMedCrossRefGoogle Scholar
  28. Tang H, Kambris Z, Lemaitre B, Hashimoto C (2008) A serpin that regulates immune melanization in the respiratory system of Drosophila. Dev Cell 15(4):617–626PubMedCrossRefGoogle Scholar
  29. Venken KJ, Bellen HJ (2007) Transgenesis upgrades for Drosophila melanogaster. Development 134(20):3571–3584PubMedCrossRefGoogle Scholar
  30. Venken KJ, Carlson JW, Schulze KL, Pan H, He Y, Spokony R, Wan KH, Koriabine M, de Jong PJ, White KP, Bellen HJ, Hoskins RA (2009) Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster. Nat Methods 6(6):431–434PubMedCrossRefGoogle Scholar
  31. Vercelli D (2008) Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 8(3):169–182PubMedCrossRefGoogle Scholar
  32. Wagner C, Isermann K, Fehrenbach H, Roeder T (2008) Molecular architecture of the fruit fly’s airway epithelial immune system. BMC Genomics 9:446PubMedCrossRefGoogle Scholar
  33. Wagner C, Isermann K, Roeder T (2009) Infection induces a survival program and local remodeling in the airway epithelium of the fly. FASEB J 23(7):2045–2054PubMedCrossRefGoogle Scholar
  34. Whitten J (1957) The post-embryonic development of the tracheal system in Drosophila melanogaster. Q J Microsc Sci 98:123–150Google Scholar
  35. Wolf MJ, Amrein H, Izatt JA, Choma MA, Reedy MC, Rockman HA (2006) Drosophila as a model for the identification of genes causing adult human heart disease. Proc Natl Acad Sci USA 103:1394–1399PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Thomas Roeder
    • 1
  • Kerstin Isermann
    • 1
  • Kim Kallsen
    • 2
  • Karin Uliczka
    • 2
  • Christina Wagner
    • 3
  1. 1.Christian-Albrechts University KielKielGermany
  2. 2.Research Center BorstelBorstelGermany
  3. 3.University Hospital EppendorfHamburgGermany

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