Global Health Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15966-71. doi: 10.1073/pnas.1105994108. Epub 2011 Sep 6.
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.
围食膜（PM）形成了一层由几丁质和糖蛋白组成的结构，排列在昆虫肠道腔的表面。这个物理屏障在功能上类似于脊椎动物消化道的黏液分泌，被认为可以保护中肠上皮免受磨损的食物颗粒和微生物的侵害。关于 PM 在果蝇中的功能几乎一无所知，而且其作为免疫屏障的功能从未通过遗传方法得到解决。在这里，我们表明 Drosocrystallin（Dcy）蛋白，一种果蝇眼睛晶状体的假定成分，有助于成体 PM 的形成。dcy 基因的功能丧失突变会导致 PM 宽度减小，通透性增加。在摄入细菌后，抗菌肽的表达水平升高，这表明这种基质对 Imd 免疫途径中细菌的感应有影响。此外，dcy 缺陷型果蝇对食源性细菌如绿僵菌和粘质沙雷氏菌的口腔感染更为敏感。缺乏 Dcy 的果蝇在摄入绿僵菌有毒提取物后比野生型果蝇更快地死亡。我们表明，这种致死性部分是由于一种叫做 Monalysin 的孔形成毒素的有害作用增加所致，这种毒素是绿僵菌产生的。总之，我们对 dcy 免疫表型的分析表明，PM 在果蝇宿主抵御肠道病原体的防御中起着重要作用，防止了孔形成毒素对肠道细胞的破坏性作用。
