Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2.
Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2.
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DOI：
10.1371/journal.ppat.0020014
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发表时间：
2006-02
期刊：
影响因子：
6.7
通讯作者：
Royet J
中科院分区：
文献类型：
--
作者：
Bischoff V;Vignal C;Duvic B;Boneca IG;Hoffmann JA;Royet J
肽聚糖识别蛋白（PGRP）是进化上保守的分子，在结构上与细菌酰胺酶相关。一些果蝇PGRP已经失去了这种酶活性，并通过肽聚糖识别作为微生物传感器。其他PGRP家族成员，如果蝇PGRP-SC 1或哺乳动物PGRP-L，具有保守的酰胺酶功能，并能够在体外切割肽聚糖。然而，这些酰胺酶PGRP对宿主体内防御的贡献迄今为止仍然难以捉摸。使用RNA干扰的方法，我们解决了两个PGRP与酰胺酶活性在果蝇免疫反应的功能。我们观察到，PGRP-SC 1/2-耗尽的苍蝇呈现出一个特定的过度激活的IMD（免疫缺陷）信号通路后，细菌的挑战。我们的数据表明，这些蛋白质在幼虫肠道中起作用，以防止细菌摄入后激活这一途径。我们进一步表明，严格控制IMD途径的激活是必不可少的，以防止细菌诱导的发育缺陷和幼虫死亡。人们早就知道哺乳动物的免疫反应需要严格控制。反应延迟或活力不足可能导致无法控制感染。然而，过度或不适当的炎症可能是有害的或致命的。果蝇作为一个模型，证据表明，这种免疫调节也是必不可少的无脊椎动物和介导的肽聚糖识别蛋白（PGRP）。PGRP是来源于裂解细菌肽聚糖的酶的进化上保守的分子。先前已经表明，一些PGRP已经失去了这种酶活性和作为果蝇免疫途径上游细菌传感器的功能。迄今为止，保持酶活性的PGRP对宿主防御的贡献仍然难以捉摸。在这里，作者研究了果蝇PGRP与酶活性的作用在体内的数据。他们的研究结果表明，这些蛋白质是幼虫肠道所需的，以负调节免疫反应，从而防止细菌诱导的发育缺陷和死亡。
Peptidoglycan-recognition proteins (PGRPs) are evolutionarily conserved molecules that are structurally related to bacterial amidases. Several Drosophila PGRPs have lost this enzymatic activity and serve as microbe sensors through peptidoglycan recognition. Other PGRP family members, such as Drosophila PGRP-SC1 or mammalian PGRP-L, have conserved the amidase function and are able to cleave peptidoglycan in vitro. However, the contribution of these amidase PGRPs to host defense in vivo has remained elusive so far. Using an RNA-interference approach, we addressed the function of two PGRPs with amidase activity in the Drosophila immune response. We observed that PGRP-SC1/2–depleted flies present a specific over-activation of the IMD (immune deficiency) signaling pathway after bacterial challenge. Our data suggest that these proteins act in the larval gut to prevent activation of this pathway following bacterial ingestion. We further show that a strict control of IMD-pathway activation is essential to prevent bacteria-induced developmental defects and larval death. It has long been known that the mammalian immune response needs to be kept under tight control. Responses that are delayed or of insufficient vigor can lead to a failure to control infection. However, excessive or inappropriate inflammation can be harmful or event fatal. Using the fruit fly as a model, evidence is presented that such an immuno-modulation is also essential in invertebrates and is mediated by peptidoglycan-recognition proteins (PGRPs). PGRPs are evolutionarily conserved molecules derived from enzymes that cleave bacterial peptidoglycan. It has been shown previously that some PGRPs have lost this enzymatic activity and function as sensors of bacteria upstream of the Drosophila immune pathways. The contribution of PGRPs which have maintained enzymatic activity to host defense has remained elusive so far. Here, the authors investigate in vivo data on the role of Drosophila PGRPs with enzymatic activity. Their results suggest that these proteins are required in the larval gut to negatively regulate the immune response, thus preventing bacterially induced developmental defects and death.