Journal
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Volume 39, Issue 3, Pages 188-197Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2012.10.007
Keywords
Imd pathway; Innate immunity; Drosophila; NF-kappa B signaling; zfh1
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Funding
- Finnish Academy
- Pirkanmaa Hospital District
- Sigrid Juselius Foundation
- Finnish Cultural Foundation
- Maud Kuistila Memorial Foundation
- Biocenter Finland
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The fruit fly Drosophila melanogaster has a powerful innate immune system, which culminates on the synthesis of potent antimicrobial peptides (AMPs). This is mainly controlled by two conserved signaling cascades, the Toll and the immune deficiency (Imd) pathways. Like in humans, Drosophila immune responses need to be under tight control at multiple levels to avoid harmful inflammation. We have identified the transcription factor Zn finger homeodomain 1 (zfh1) as a negative regulator of Drosophila Imd signaling. Knocking down zfh1 in Drosophila S2 cells hyperactivates Imd pathway-mediated AMP expression, whereas forced zfh1 expression blocks Imd pathway response downstream of, or parallel to, the Imd pathway transcription factor Relish. In vivo zfh1 RNAi hyperactivates CecropinB induction upon gram-negative bacterial infection. We conclude that zfh1 is an important regulator of the immune response in Drosophila. (C) 2012 Elsevier Ltd. All rights reserved.
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