Institute of Biomedical Technology and BioMediTech, University of Tampere, Finland.
Dev Comp Immunol. 2013 Mar;39(3):188-97. doi: 10.1016/j.dci.2012.10.007. Epub 2012 Nov 23.
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.
黑腹果蝇（Drosophila melanogaster）具有强大的先天免疫系统，其最终表现为强效抗菌肽（AMPs）的合成。这主要由两个保守的信号级联反应，即 Toll 和免疫缺陷（Imd）途径所控制。与人类相似，果蝇的免疫反应需要在多个层面上受到严格控制，以避免有害的炎症。我们已经确定转录因子 Zn 指同源结构域 1（zfh1）是果蝇 Imd 信号的负调控因子。在果蝇 S2 细胞中敲低 zfh1 会过度激活 Imd 途径介导的 AMP 表达，而强制表达 zfh1 会阻断 Relish 等 Imd 途径转录因子下游或平行的 Imd 途径反应。体内 RNAi 敲低 zfh1 会在革兰氏阴性细菌感染时过度激活 CecropinB 的诱导。我们得出结论，zfh1 是果蝇免疫反应的重要调节因子。
