Differential activation of the NF-κB-like factors relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria
Differential activation of the NF-κB-like factors relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria
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DOI：
10.1074/jbc.m313856200
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发表时间：
2004-05-14
影响因子：
4.8
通讯作者：
Taylor, BJ
中科院分区：
文献类型：
--
作者：
Hedengren-Olcott, M;Olcott, MC;Taylor, BJ
目前的果蝇免疫激活模型表明，真菌和革兰氏阳性（G（+））细菌激活Toll/Dif途径，革兰氏阴性（G（-））细菌激活Imd/Relish途径。为了测试该模型，我们检查了Relish和Dif（Dorsal-related immunity factor）突变体对各种真菌和G（+）和G（-）细菌的挑战的响应。在Relish突变体中，抗菌肽A基因被G（+）细菌藤黄微球菌和金黄色葡萄球菌诱导，但不被其他G（+）或G（-）细菌诱导。这种不依赖于食欲的天蚕素A诱导在Dif/Relish双突变果蝇中被阻断。用M.黄体需要Relish，而天蚕素A2基因的诱导需要Dif。完整的肽聚糖（PG）是这种差异诱导天蚕素A所必需的。PG是从M. Luteus在Relish突变体中诱导天蚕素A，而来自G（+）细菌巨大芽孢杆菌和枯草芽孢杆菌的PG则没有，这表明果蝇的免疫系统可以区分来自各种G（+）细菌的PG。各种真菌通过至少两种不同的途径刺激抗菌肽，需要Relish和/或Dif。白地霉诱导Attacin A需要Relish，而球孢白僵菌激活Attacin A需要Dif，这表明果蝇的免疫系统至少可以区分这两种真菌。我们的结论是，果蝇的免疫系统比目前的模型更复杂。我们提出了一个新的模型来解释这种免疫系统的复杂性，将果蝇免疫系统的不同模式识别受体，它可以区分各种真菌和G（+）细菌，从而导致选择性诱导的抗菌肽通过不同的激活Relish和Dif。
The current model of immune activation in Drosophila melanogaster suggests that fungi and Gram-positive (G(+)) bacteria activate the Toll/Dif pathway and that Gram-negative (G(-)) bacteria activate the Imd/Relish pathway. To test this model, we examined the response of Relish and Dif (Dorsal-related immunity factor) mutants to challenge by various fungi and G(+) and G(-) bacteria. In Relish mutants, the Cecropin A gene was induced by the G(+) bacteria Micrococcus luteus and Staphylococcus aureus, but not by other G(+) or G(-) bacteria. This Relish-independent Cecropin A induction was blocked in Dif/Relish double mutant flies. Induction of the Cecropin A1 gene by M. luteus required Relish, whereas induction of the Cecropin A2 gene required Dif. Intact peptidoglycan (PG) was necessary for this differential induction of Cecropin A. PG extracted from M. luteus induced Cecropin A in Relish mutants, whereas PGs from the G(+) bacteria Bacillus megaterium and Bacillus subtilis did not, suggesting that the Drosophila immune system can distinguish PGs from various G(+) bacteria. Various fungi stimulated antimicrobial peptides through at least two different pathways requiring Relish and/or Dif. Induction of Attacin A by Geotrichum candidum required Relish, whereas activation by Beauvaria bassiana required Dif, suggesting that the Drosophila immune system can distinguish between at least these two fungi. We conclude that the Drosophila immune system is more complex than the current model. We propose a new model to account for this immune system complexity, incorporating distinct pattern recognition receptors of the Drosophila immune system, which can distinguish between various fungi and G(+) bacteria, thereby leading to selective induction of antimicrobial peptides via differential activation of Relish and Dif.