Abstract
The common fruit fly Drosophila melanogaster is a powerful model for studying signaling pathway regulation. Conserved signaling pathways underlying physiological processes signify evolutionary relationship between organisms and the nature of the mechanisms they control. This study explores the cross-talk between the well-characterized nuclear factor kappa B (NF-κB) innate immune signaling pathways and transforming growth factor beta (TGF-β) signaling pathway in response to parasitic nematode infection in Drosophila. To understand the link between signaling pathways, we followed on our previous studies by performing a transcript-level analysis of different TGF-β signaling components following infection of immune-compromised Drosophila adult flies with the nematode parasites Heterorhabditis gerrardi and H. bacteriophora. Our findings demonstrate the requirement of NF-κB transcription factors for activation of TGF-β signaling pathway in Drosophila in the context of parasitic nematode infection. We observe significant decrease in transcript level of glass bottom boat (gbb) and screw (scw), components of the bone morphogenic protein (BMP) branch, as well as Activinβ (actβ) which is a component of the Activin branch of the TGF-β signaling pathway. These results are observed only in H. gerrardi nematode-infected flies compared to uninfected control. Also, this significant decrease in transcript level is found only for extracellular ligands. Future research examining the mechanisms regulating the interaction of these signaling pathways could provide further insight into Drosophila anti-nematode immune function against infection with potent parasitic nematodes.




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Acknowledgements
We thank Kyle Devine for maintaining the Drosophila stocks and members of the Department of Biological Sciences at GWU for critical reading of the manuscript. We thank Dr. Jean-Marc Reichhart (National Center for Scientific Research, Strasbourg, France) and Dr. Louisa Wu (University of Maryland, College Park, USA) for providing us with fly immune mutant lines.
Funding
This work was funded by the National Institute of Allergy and Infectious Diseases (grant 1R01AI110675–01A1 and 1R56AI110675-01).
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Patrnogic, J., Heryanto, C., Ozakman, Y. et al. Transcript analysis reveals the involvement of NF-κB transcription factors for the activation of TGF-β signaling in nematode-infected Drosophila. Immunogenetics 71, 501–510 (2019). https://doi.org/10.1007/s00251-019-01119-8
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DOI: https://doi.org/10.1007/s00251-019-01119-8