Transcription factor zfh1 downregulates Drosophila Imd pathway

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.

► Zfh1 is a new negative regulator of Drosophila Imd signaling.
► Zfh1 downregulates Imd pathway at transcriptional level.
► In vivo zfh1 RNAi hyperactivates CecropinB induction upon bacterial infection.
► Human homologue of zfh1, ZEB1, regulates TNFR signaling in HeLa cells.