Tissue-Specific Regulation of Drosophila NF-κB Pathway Activation by Peptidoglycan Recognition Protein SC
Tissue-Specific Regulation of Drosophila NF-κB Pathway Activation by Peptidoglycan Recognition Protein SC
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DOI：
10.1159/000437368
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发表时间：
2016-01-01
影响因子：
5.3
通讯作者：
Royet, Julien
中科院分区：
文献类型：
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作者：
Costechareyre, Denis;Capo, Florence;Royet, Julien
在果蝇中，肽聚糖 (PGN) 通过充当模式识别受体的 PGN 识别蛋白 (PGRP) 进行检测。一些 PGRP（例如 PGRP-LB 或 PGRP-SC）能够裂解 PGN，从而减少免疫诱导子的数量并抑制免疫缺陷 (IMD) 途径的激活。 PGRP-SC 的确切作用尚不清楚，因为 PGRP-SC 基因（PGRP-SC1a、PGRP-SC1b 和 PGRP-SC2）位于染色体上非常接近，并且已使用包含这三个基因的缺失进行了研究。通过生成 PGRP-SC 特异性突变体，我们分别重新评估了 PGRP-LB、PGRP-SC1 和 PGRP-SC2 在免疫反应过程中的作用。我们发现这些基因在不同的肠道域中表达，并且它们遵循不同的转录调控。功能缺失突变体分析表明，尽管 PGRP-SC 在肠道中高水平表达，但 PGRP-LB 在肠道内 IMD 途径激活和细菌负荷调节中发挥着重要作用。我们还证明 PGRP-SC2 是脂肪体内 IMD 通路激活的主要负调节因子。因此，我们发现 PGRP-LB 或 PGRP-SC2 的突变体根据感染途径对细菌表现出不同的敏感性。最后，我们证明了革兰氏阳性菌在体内完全激活 Toll 途径需要 PGRP-SC1 和 PGRP-SC2。 (C) 2015 S. Karger AG，巴塞尔
In Drosophila, peptidoglycan (PGN) is detected by PGN recognition proteins (PGRPs) that act as pattern recognition receptors. Some PGRPs such as PGRP-LB or PGRP-SCs are able to cleave PGN, therefore reducing the amount of immune elicitors and dampening immune deficiency (IMD) pathway activation. The precise role of PGRP-SC is less well defined because the PGRP-SC genes (PGRP-SC1a, PGRP-SC1b and PGRP-SC2) lie very close on the chromosome and have been studied using a deletion encompassing the three genes. By generating PGRP-SC-specific mutants, we reevaluated the roles of PGRP-LB, PGRP-SC1 and PGRP-SC2, respectively, during immune responses. We showed that these genes are expressed in different gut domains and that they follow distinct transcriptional regulation. Loss-of-function mutant analysis indicates that PGRP-LB is playing a major role in IMD pathway activation and bacterial load regulation in the gut, although PGRP-SCs are expressed at high levels in this organ. We also demonstrated that PGRP-SC2 is the main negative regulator of IMD pathway activation in the fat body. Accordingly, we showed that mutants for either PGRP-LB or PGRP-SC2 displayed a distinct susceptibility to bacteria depending on the infection route. Lastly, we demonstrated that PGRP-SC1 and PGRP-SC2 are required in vivo for full Toll pathway activation by Gram-positive bacteria. (C) 2015 S. Karger AG, Basel