Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model.
Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model.
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DOI：
10.1371/journal.ppat.0020056
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发表时间：
2006-06
期刊：
影响因子：
6.7
通讯作者：
Lemaitre B
中科院分区：
文献类型：
--
作者：
Liehl P;Blight M;Vodovar N;Boccard F;Lemaitre B
病原体已经开发出多种策略，使它们能够利用宿主资源并抵抗免疫反应。为了研究果蝇在自然环境中如何应对传染病，我们研究了果蝇和一种新发现的昆虫病原体--嗜虫假单胞菌之间的相互作用。尽管诱导了局部和全身免疫应答，但经口感染嗜虫假单胞菌的苍蝇迅速死亡，表明该细菌已发展出逃避苍蝇免疫应答的特异性策略。使用对宿主和病原体的组合遗传方法，我们表明，嗜虫单胞菌毒力是多因素的，触发免疫反应的因素和促进致病性的因素之间存在明显的差异。我们证明AprA是一种分泌型金属蛋白酶，是一种重要的毒力因子。aprA的失活减弱了在宿主中持续存在的能力和致病性。有趣的是，aprA突变体能够在免疫缺陷的Relish果蝇中存活至野生型水平，表明蛋白酶在保护果蝇免疫应答中起重要作用。我们的研究还表明，果蝇对嗜虫单胞菌防御的主要贡献是由局部免疫反应提供的，而不是全身免疫反应。更确切地说，我们的数据指出了抗微生物肽Diptericin对口腔感染性革兰氏阴性菌的重要作用，强调了局部抗微生物肽表达对食源性病原体的关键作用。正常的进食和消化涉及许多微生物的摄入。许多是无害的，一些是有害的，而另一些可能是致病的。因此，真核生物已经进化出复杂的机制来检测、控制，并在必要时消除肠道微生物。昆虫也不例外，果蝇（Drosophila）在肠腔和围食基质内采用物理屏障，以及表现出与哺乳动物对应物相似的先天免疫反应。嗜虫假单胞菌（Pseudomonasentomophila）是一种新的昆虫病原细菌，能感染果蝇肠道并在肠道内定殖。在这篇论文中，Liehl等人描述了嗜虫假单胞菌的一种特异性分泌毒力因子，锌金属蛋白酶AprA，他们证明这是防御宿主肠道上皮免疫反应所必需的。AprA保护嗜虫毕赤酵母抵抗由肠道先天免疫应答产生的果蝇抗微生物肽。嗜虫假单胞菌aprA突变体在野生型果蝇中的毒力减弱，但在不表达这些抗微生物肽的免疫缺陷突变果蝇中与野生型细菌一样具有感染性。虽然分泌的蛋白酶先前已被描述为针对宿主免疫蛋白的潜在重要防御，但这是针对昆虫抗微生物肽的这种特异性作用的体内证明的罕见实例之一。
Pathogens have developed multiple strategies that allow them to exploit host resources and resist the immune response. To study how Drosophila flies deal with infectious diseases in a natural context, we investigated the interactions between Drosophila and a newly identified entomopathogen, Pseudomonas entomophila. Flies orally infected with P. entomophila rapidly succumb despite the induction of both local and systemic immune responses, indicating that this bacterium has developed specific strategies to escape the fly immune response. Using a combined genetic approach on both host and pathogen, we showed that P. entomophila virulence is multi-factorial with a clear differentiation between factors that trigger the immune response and those that promote pathogenicity. We demonstrate that AprA, an abundant secreted metalloprotease produced by P. entomophila, is an important virulence factor. Inactivation of aprA attenuated both the capacity to persist in the host and pathogenicity. Interestingly, aprA mutants were able to survive to wild-type levels in immune-deficient Relish flies, indicating that the protease plays an important role in protection against the Drosophila immune response. Our study also reveals that the major contribution to the fly defense against P. entomophila is provided by the local, rather than the systemic immune response. More precisely, our data points to an important role for the antimicrobial peptide Diptericin against orally infectious Gram-negative bacteria, emphasizing the critical role of local antimicrobial peptide expression against food-borne pathogens. Normal feeding and digestion involves the ingestion of many microorganisms. Many are innocuous, some are commensal, and others may be pathogenic. Eukaryotes have thus evolved complex mechanisms to detect, control, and if necessary, eliminate intestinal microbes. Insects are no exception, and the fruit fly, Drosophila, employs a physical barrier within the intestinal lumen and the peritrophic matrix, and an innate immune response which exhibits similarities to the mammalian counterpart. Pseudomonas entomophila was identified as a novel entomopathogenic bacterium that can infect and colonize the gut of Drosophila. In this paper, Liehl et al. describe one specific secreted virulence factor of P. entomophila, the zinc metalloprotease, AprA, which they demonstrate to be required for defense against the host gut epithelial immune response. AprA defends P. entomophila against the Drosophila antimicrobial peptides, produced by the gut innate immune response. P. entomophila aprA mutants are attenuated for virulence in wild-type Drosophila but are equally infective as wild-type bacteria in immune-deficient mutant flies that do not express these antimicrobial peptides. Although secreted proteases have previously been described as a potentially important defense against host immune proteins, this is one of the rare examples of an in vivo demonstration of such a specific role against insect antimicrobial peptides.
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影响因子：
11.4
作者：
Ferrandon, D;Jung, AC;Hoffmann, JA
通讯作者：
Hoffmann, JA
影响因子：
3.2
作者：
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DOI：
10.1073/pnas.070357597
发表时间：
2000-03-28
影响因子：
11.1
作者：
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通讯作者：
Lemaitre, B
影响因子：
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作者：
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通讯作者：
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影响因子：
11.8
作者：
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通讯作者：
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