In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the Defense against Gram-positive bacterial infection in Drosophila adults
In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the Defense against Gram-positive bacterial infection in Drosophila adults
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DOI：
10.1074/jbc.m313324200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Lemaitre, B
中科院分区：
文献类型：
--
作者：
Pili-Floury, S;Leulier, F;Lemaitre, B
果蝇的免疫系统区分不同类别的感染微生物，通过选择性地激活Toll和免疫缺陷(IMD)信号通路来响应病原体特异性的防御反应。Toll途径介导了大多数对革兰氏阳性细菌和真菌的防御，而IMD途径是抵抗革兰氏阴性细菌感染所必需的。微生物的识别是通过肽聚糖识别蛋白(PGRP)实现的；革兰氏阳性细菌通过循环的PGRP-SA(PGRP-SA)激活Toll途径，而革兰氏阴性菌通过可能的跨膜受体PGRP-LC和PGRP-LE激活IMD途径。革兰氏阴性结合蛋白(GNBPs)最初在家蚕中被发现，是因为它们能够结合各种微生物化合物。果蝇基因组中编码了三个GNBPs和两个相关蛋白，但它们的功能尚不清楚。利用GNBP1双链RNA的诱导表达，我们现在证明了GNBP1是响应革兰氏阳性细菌感染而激活Toll所必需的；GNBP1双链RNA的表达使果蝇对革兰氏阳性细菌感染易感，并在革兰氏阳性细菌感染后减少了抗真菌多肽编码基因Drosmycin的诱导，但在真菌感染后不减少。这种由GNBP1失活引起的表型与PGRP-SA的功能丧失突变相同，我们的遗传学研究表明GNBP1作用于Toll配体Spatzle的上游。总之，我们的结果表明，在果蝇中检测革兰氏阳性细菌需要两个假定的模式识别受体，PGRP-SA和GNBP1。
The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions via the selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi, whereas the Imd pathway is required to resist Gram-negative bacterial infection. Microbial recognition is achieved through peptidoglycan recognition proteins (PGRPs); Gram-positive bacteria activate the Toll pathway through a circulating PGRP (PGRP-SA), and Gram-negative bacteria activate the Imd pathway via PGRP-LC, a putative transmembrane receptor, and PGRP-LE. Gram-negative binding proteins (GNBPs) were originally identified in Bombyx mori for their capacity to bind various microbial compounds. Three GNBPs and two related proteins are encoded in the Drosophila genome, but their function is not known. Using inducible expression of GNBP1 double-stranded RNA, we now demonstrate that GNBP1 is required for Toll activation in response to Gram-positive bacterial infection; GNBP1 double-stranded RNA expression renders flies susceptible to Gram-positive bacterial infection and reduces the induction of the antifungal peptide encoding gene Drosomycin after infection by Gram-positive bacteria but not after fungal infection. This phenotype induced by GNBP1 inactivation is identical to a loss-of-function mutation in PGRP-SA, and our genetic studies suggest that GNBP1 acts upstream of the Toll ligand Spatzle. Altogether, our results demonstrate that the detection of Gram-positive bacteria in Drosophila requires two putative pattern recognition receptors, PGRP-SA and GNBP1.