Inducible expression of double-stranded RNA reveals a role for dFADD in the regulation of the antibacterial response in Drosophila adults
Inducible expression of double-stranded RNA reveals a role for dFADD in the regulation of the antibacterial response in Drosophila adults
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DOI：
10.1016/s0960-9822(02)00873-4
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发表时间：
2002-06-25
期刊：
影响因子：
9.2
通讯作者：
Lemaitre, B
中科院分区：
文献类型：
--
作者：
Leulier, F;Vidal, S;Lemaitre, B
在果蝇中，免疫缺陷（Imd）途径控制脂肪体中响应革兰氏阴性细菌感染的抗菌肽基因表达[1，2]。Imd通路的最终靶点是Relish，一种与哺乳动物P105和P100 NF-κ B前体相关的反式激活因子[3]。加工Relish以易位到细胞核，并且这种切割依赖于Dredd（与哺乳动物的半胱天冬酶-8相关的顶端半胱天冬酶）和苍蝇Ikappa-B激酶复合物（dmIKK）[4-9]。dTAK 1是一种MAPKKK，在dmIKK复合物的上游和Imd的下游发挥作用，Imd是一种具有与哺乳动物受体相互作用蛋白（RIP）相似的死亡结构域的蛋白质[10，11]。最后，肽聚糖识别蛋白-LC（PGRP-LC）在Imd的上游起作用，可能作为Imd途径的受体发挥作用[12-14]。使用dFADD双链RNA的诱导表达，我们证明了dFADD是Imd途径的一个新的组成部分：dFADD双链RNA表达减少了感染后抗菌肽编码基因的诱导，并使苍蝇容易受到革兰氏阴性细菌感染。上位性研究表明dFADD作用于Imd和Dredd之间。我们的研究结果加强了Imd和TNF-R1途径之间的相似性。
In Drosophila, the immune deficiency (Imd) pathway controls antibacterial peptide gene expression in the fat body in response to Gram-negative bacterial infection [1, 2]. The ultimate target of the Imd pathway is Relish, a transactivator related to mammalian P105 and P100 NF-kappaB precursors [3]. Relish is processed in order to translocate to the nucleus, and this cleavage is dependent on both Dredd, an apical caspase related to caspase-8 of mammals, and the fly Ikappa-B kinase complex (dmIKK) [4-9]. dTAK1, a MAPKKK, functions upstream of the dmIKK complex and downstream of Imd, a protein with a death domain similar to that of mammalian receptor interacting protein (RIP) [10, 11]. Finally, the peptidoglycan recognition protein-LC (PGRP-LC) acts upstream of Imd and probably functions as a receptor for the Imd pathway [12-14]. Using inducible expression of dFADD double-stranded RNA, we demonstrate that dFADD is a novel component of the Imd pathway: dFADD double-stranded RNA expression reduces the induction of antibacterial peptide-encoding genes after infection and renders the fly susceptible to Gram-negative bacterial infection. Epistatic studies indicate that dFADD acts between Imd and Dredd. Our results reinforce the parallels between the Imd and the TNF-R1 pathways.