The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection

被引:401
作者
Zaidman-Remy, A
Herve, M
Poidevin, M
Pili-Floury, S
Kim, MS
Blanot, D
Oh, BH
Ueda, R
Mengin-Lecreulx, D
Lemaitre, B [1 ]
机构
[1] CNRS, Ctr Genet Mol, F-91198 Gif Sur Yvette, France
[2] Univ Paris 11, CNRS, UMR 8619, Inst Biochim & Biophys Mol & Cellulaire, F-91405 Orsay, France
[3] Pohang Univ Sci & Technol, Dept Life Sci, Ctr Biomol Recognit, Pohang 790784, Kyungbuk, South Korea
[4] Natl Inst Genet, Shizuoka 4118540, Japan
关键词
D O I
10.1016/j.immuni.2006.02.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:463 / 473
页数:11
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