Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster
Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster
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DOI：
10.1073/pnas.1105994108
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发表时间：
2011-09-20
影响因子：
11.1
通讯作者：
Lemaitre, Bruno
中科院分区：
文献类型：
--
作者：
Kuraishi, Takayuki;Binggeli, Olivier;Lemaitre, Bruno
围食基质（PM）形成一层由几丁质和糖蛋白组成的衬在昆虫肠腔内的层。这种物理屏障的作用类似于脊椎动物消化道的粘液分泌物，被认为是保护中肠上皮免受磨蚀性食物颗粒和微生物的侵害。几乎没有人知道果蝇的PM功能，它作为免疫屏障的功能从来没有被遗传学方法解决过。在这里，我们表明，Drosocrystallin（Dcy）蛋白，果蝇的眼睛透镜的推定组成部分，有助于成人PM的形成。dcy基因的功能丧失突变导致PM宽度减少和其渗透性增加。在细菌摄入后，在dcy突变体中观察到更高水平的抗菌肽表达，这表明该基质对Imd免疫途径的细菌传感的影响。此外，dcy缺陷的苍蝇表现出对昆虫病原细菌嗜虫假单胞菌和粘质沙雷氏菌的口腔感染的易感性增加。在摄入嗜虫假单胞菌毒性提取物后，Dcy突变型果蝇也比野生型更快地死亡。我们表明，这种致死性部分是由于增加有害作用的Monalysin，一个孔形成毒素产生的P.虫。总的来说，我们的dcy免疫表型的分析表明，PM起着重要的作用，在果蝇宿主防御肠道病原体，防止肠道细胞上的致孔毒素的破坏作用。
The peritrophic matrix (PM) forms a layer composed of chitin and glycoproteins that lines the insect intestinal lumen. This physical barrier plays a role analogous to that of mucous secretions of the vertebrate digestive tract and is thought to protect the midgut epithelium from abrasive food particles and microbes. Almost nothing is known about PM functions in Drosophila, and its function as an immune barrier has never been addressed by a genetic approach. Here we show that the Drosocrystallin (Dcy) protein, a putative component of the eye lens of Drosophila, contributes to adult PM formation. A loss-of-function mutation in the dcy gene results in a reduction of PM width and an increase of its permeability. Upon bacterial ingestion a higher level of expression of antibacterial peptides was observed in dcy mutants, pointing to an influence of this matrix on bacteria sensing by the Imd immune pathway. Moreover, dcy-deficient flies show an increased susceptibility to oral infections with the entomopathogenic bacteria Pseudomonas entomophila and Serratia marcescens. Dcy mutant flies also succumb faster than wild type upon ingestion of a P. entomophila toxic extract. We show that this lethality is due in part to an increased deleterious action of Monalysin, a pore-forming toxin produced by P. entomophila. Collectively, our analysis of the dcy immune phenotype indicates that the PM plays an important role in Drosophila host defense against enteric pathogens, preventing the damaging action of pore-forming toxins on intestinal cells.