Bischoff Vincent, Vignal Cécile, Duvic Bernard, Boneca Ivo G, Hoffmann Jules A, Royet Julien
Institut de Biologie Moléculaire et Cellulaire, UPR 9022 du CNRS, Strasbourg, France.
PLoS Pathog. 2006 Feb;2(2):e14. doi: 10.1371/journal.ppat.0020014. Epub 2006 Feb 24.
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.
肽聚糖识别蛋白（PGRPs）是进化上保守的分子，在结构上与细菌酰胺酶相关。几种果蝇PGRPs已失去这种酶活性，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-SC1或哺乳动物PGRP-L，保留了酰胺酶功能，并且能够在体外切割肽聚糖。然而，迄今为止，这些酰胺酶PGRPs在体内对宿主防御的贡献仍不清楚。我们使用RNA干扰方法研究了两种具有酰胺酶活性的PGRPs在果蝇免疫反应中的功能。我们观察到，在细菌攻击后，PGRP-SC1/2缺失的果蝇呈现出IMD（免疫缺陷）信号通路的特异性过度激活。我们的数据表明，这些蛋白质在幼虫肠道中起作用，以防止细菌摄入后该通路的激活。我们进一步表明，严格控制IMD通路的激活对于防止细菌诱导的发育缺陷和幼虫死亡至关重要。
