The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection
The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection
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DOI：
10.1016/j.immuni.2006.02.012
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发表时间：
2006-04-01
期刊：
影响因子：
32.4
通讯作者：
Lemaitre, B
中科院分区：
文献类型：
--
作者：
Zaidman-Remy, A;Herve, M;Lemaitre, B
果蝇宿主对革兰氏阴性细菌的防御是由肽聚糖识别蛋白 (PGRP)-LC 感知肽聚糖后的 Imd 途径介导的。在这里，我们报告了 PGRP-LB（PGRP 家族的催化成员）的功能分析。我们证明 PGRP-LB 是一种受 Imd 途径调节的分泌蛋白。生化研究表明 PGRP-LB 是一种酰胺酶，可特异性降解革兰氏阴性菌肽聚糖。与其酰胺酶活性一致，PGRP-LB 下调 Imd 途径。因此，Imd 途径激活 PGRP-LB 提供了负反馈调节，以紧密调节针对感染的免疫激活。我们的研究还表明，PGRP-LB 控制果蝇对肠道中摄入细菌的免疫反应。我们的工作强调了编码肽聚糖传感器和清除剂的 PGRP 的关键作用，它们调节宿主对传染性微生物存在的免疫反应水平。
The Drosophila host defense against gram-negative bacteria is mediated by the Imd pathway upon sensing of peptidoglycan by the peptidoglycan recognition protein (PGRP)-LC. Here we report a functional analysis of PGRP-LB, a catalytic member of the PGRP family. We show that PGRP-LB is a secreted protein regulated by the Imd pathway. Biochemical studies demonstrate that PGRP-LB is an amidase that specifically degrades gram-negative bacteria peptidoglycan. In agreement with its amidase activity, PGRP-LB downregulates the Imd pathway. Hence, activation of PGRP-LB by the Imd pathway provides a negative feedback regulation to tightly adjust immune activation to infection. Our study also reveals that PGRP-LB controls the immune reactivity of flies to the presence of ingested bacteria in the gut. Our work highlights the key role of PGRPs that encode both sensors and scavengers of peptidoglycan, which modulate the level of the host immune response to the presence of infectious microorganisms.