Identification of drosophila mutants altering defense of and endurance to Listeria monocytogenes infection
Identification of drosophila mutants altering defense of and endurance to Listeria monocytogenes infection
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DOI：
10.1534/genetics.107.083782
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发表时间：
2008-03-01
期刊：
影响因子：
3.3
通讯作者：
Schneider, David S.
中科院分区：
文献类型：
--
作者：
Ayres, Janelle S.;Freitag, Nancy;Schneider, David S.
我们扩展了果蝇的使用范围，使其不仅仅是模式识别免疫信号所需的信号通路的模型，并表明果蝇可用于识别致病和宿主-病原体相互作用所需的基因。我们进行了正向遗传筛选，以确定果蝇突变改变细胞内病原体单核细胞增生李斯特菌的敏感性。我们回收了18个突变体，这些突变体对感染的易感性增加，以前没有一个在果蝇免疫反应中发挥作用。使用二次筛选，我们将这些突变体分为两组。这是一个新的苍蝇免疫表型，是不常见的研究。在第二组中，突变体对L.单核细胞增多症突变体，我们确定了影响特定阶段的L。单核细胞增生的生命周期，退出液泡，或肌动蛋白为基础的运动。我们的基因与果蝇S2细胞中鉴定的数百个对抗L.单核细胞增多症感染，使用体外全基因组RNAi筛选。通过使用整个动物模型和筛选宿主存活，我们揭示了与先前筛选中发现的生理学不同的基因，这些基因在防御性免疫信号传导中都有缺陷。
We extended the use of Drosophila beyond being a model for signaling pathways required for pattern recognition immune signaling and show that the fly can be used to identify genes required for patho-genesis and host-pathogen interactions. We performed a forward genetic screen to identify Drosophila mutations altering sensitivity to the intracellular pathogen Listeria monocytogenes. We recovered 18 mutants with increased susceptibility to infection, none of which were previously shown to function in a Drosophila immune response. Using secondary screens, we divided these mutants into two groups. This is a new fly immunity phenotype that is not commonly studied. In the second group, mutants have a typical defense with L. monocytogenes mutants, we identified subgroups of fly mutants that affect specific stages of the L. monocytogenes life cycle, exit from the vacuole, or actin-based movement. There is no overlap between our genes and the hundreds of genes identified in Drosophila S2 cells fighting L. monocytogenes infection, using genomewide RNAi screens in vitro. By using a whole-animal model and screening for host survival, we revealed genes involved in physiologies different from those that were found in previous screens, which all had defects in defensive immune signaling.