Transcript analysis reveals the involvement of NF-κB transcription factors for the activation of TGF-β signaling in nematode-infected Drosophila
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.
KeywordsDrosophila Heterorhabditis Innate immunity TGF-β NF-κB Imd pathway
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.
This work was funded by the National Institute of Allergy and Infectious Diseases (grant 1R01AI110675–01A1 and 1R56AI110675-01).
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Conflict of interest
The authors declare that they have no conflict of interest.
- Arefin B, Kucerova L, Dobes P, Markus R, Strnad H, Wang Z, Hyrsl P, Zurovec M, Theopold U (2014) Genome-wide transcriptional analysis of Drosophila larvae infected by entomopathogenic nematodes shows involvement of complement, recognition and extracellular matrix proteins. J. Innate Immun. 6:192–204. https://doi.org/10.1159/000353734 CrossRefGoogle Scholar
- Ciche T (2007) The biology and genome of Heterorhabditis bacteriophora. WormBook 1(9). https://doi.org/10.1895/wormbook.1.135.1
- Ganesan, S, Aggarwal, K, Paquette, N, Silverman, N, 2011. NF-κB/Rel proteins and the humoral immune responses of Drosophila melanogaster. 25–60. https://doi.org/10.1007/82_2010_107
- Hedengren, M, Bengt, A, Dushay, MS, Ando, I, Ekengren, S, Wihlborg, M, Hultmark, D, 1999. Relish, a central factor in the control of humoral but not cellular immunity in Drosophila 4, 827–837Google Scholar
- Lemaitre B, Hoffmann J (2007) The host defense of Drosophila melanogaster. Annu Rev Immunol 25:697–743. https://doi.org/10.1146/annurev.immunol.25.022106.141615 CrossRefGoogle Scholar
- Lemaitre B, Kromer-Metzger E, Michaut L, Nicolas E, Meister M, Georgel P, Reichhart JM, Hoffmann J a (1995) A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense. Proc Natl Acad Sci U S A 92:9465–9469. https://doi.org/10.1073/pnas.92.21.9465 CrossRefGoogle Scholar
- Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA (2006) Transforming growth factor- β regulation of immune responses. Annu Rev Immunol 24:99–146. https://doi.org/10.1146/annurev.immunol.24.021605.090737 CrossRefGoogle Scholar
- Peña JM, Carrillo Ma, Hallem Ea (2015) Variation in the susceptibility of Drosophila to different entomopathogenic nematodes. Infect Immun:83. https://doi.org/10.1128/IAI.02740-14
- Rutschmann, S, Jung, a. C., Hetru, C., Reichhart, JM, Hoffmann, J. a, Ferrandon, D., 2000. The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. Immunity 12, 569–580. https://doi.org/10.1016/S1074-7613(00)80208-3
- Wan, YY, Flavell, RA, 2008. TGF-β and regulatory T cell in immunity and autoimmunity 28, 647–659. https://doi.org/10.1007/s10875-008-9251-y
- Waterfield NR, Ciche T, Clarke D (2009) Photorhabdus and a host of hosts. Annu Rev Microbiol 63:557–574. https://doi.org/10.1146/annurev.micro.091208.073507 CrossRefGoogle Scholar