Tingvall T O, Roos E, Engström Y
Department of Molecular Biology and Functional Genomics, Arrhenius Laboratories for Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3884-8. doi: 10.1073/pnas.061230198. Epub 2001 Mar 6.
Innate immunity in Drosophila is characterized by the inducible expression of antimicrobial peptides. We have investigated the development and regulation of immune responsiveness in Drosophila embryos after infection. Immune competence, as monitored by the induction of Cecropin A1-lacZ constructs, was observed first in the embryonic yolk. This observation suggests that the yolk plays an important role in the humoral immune response of the developing embryo by synthesizing antimicrobial peptides. Around midembryogenesis, the response in the yolk was diminished. Simultaneously, Cecropin expression became inducible in a large number of cells in the epidermis, demonstrating that late-stage embryos can synthesize their own antibiotics in the epidermis. This production likely serves to provide the hatching larva with an active antimicrobial barrier and protection against systemic infections. Cecropin expression in the yolk required the presence of a GATA site in the promoter as well as the involvement of the GATA-binding transcription factor Serpent (dGATAb). In contrast, neither the GATA site nor Serpent were necessary for Cecropin expression in the epidermis. Thus, the inducible immune responses in the yolk and in the epidermis can be uncoupled and call for distinct sets of transcription factors. Our data suggest that Serpent is involved in the distinction between a systemic response in the yolk/fat body and a local immune response in epithelial cells. In addition, the present study shows that signal transduction pathways controlling innate and epithelial defense reactions can be dissected genetically in Drosophila embryos.
果蝇的先天免疫以抗菌肽的可诱导表达为特征。我们研究了果蝇胚胎感染后免疫反应性的发育和调控。通过监测天蚕素A1 - lacZ构建体的诱导来检测免疫能力，首先在胚胎卵黄中观察到了这种能力。这一观察结果表明，卵黄通过合成抗菌肽在发育中胚胎的体液免疫反应中发挥重要作用。在胚胎发育中期左右，卵黄中的反应减弱。同时，天蚕素在表皮的大量细胞中变得可诱导表达，这表明晚期胚胎能够在表皮中合成自身的抗生素。这种产生可能是为了给孵化出的幼虫提供一个活跃的抗菌屏障，以抵御全身感染。卵黄中天蚕素的表达需要启动子中存在一个GATA位点以及GATA结合转录因子Serpent（dGATAb）的参与。相反，表皮中天蚕素的表达既不需要GATA位点也不需要Serpent。因此，卵黄和表皮中的可诱导免疫反应可以分开，并且需要不同的转录因子组合。我们的数据表明，Serpent参与了卵黄/脂肪体中的全身反应与上皮细胞中的局部免疫反应之间的区分。此外，本研究表明，在果蝇胚胎中可以通过遗传学方法剖析控制先天防御反应和上皮防御反应的信号转导途径。
