PDF(Pubmed)
Abstract：
Significant progress has been made in recent years on exploring immunometabolism, a field that integrates two processes essential for maintaining tissue and organismal homeostasis, immunity and metabolism. The nematode parasite Heterorhabditis gerrardi, its mutualistic bacteria Photorhabdus asymbiotica, and the fruit fly Drosophila melanogaster constitute a unique system to investigate the molecular basis of host immunometabolic response to nematode-bacterial complexes. In this study, we explored the contribution of the two major immune signaling pathways, Toll and Imd, to sugar metabolism in D. melanogaster larvae during infection with H. gerrardi nematodes. We infected Toll or Imd signaling loss-of-function mutant larvae with H. gerrardi nematodes and assessed larval survival ability, feeding rate, and sugar metabolism. We found no significant differences in the survival ability or levels of sugar metabolites in any of the mutant larvae when responding to H. gerrardi infection. However, we found that the Imd mutant larvae have higher feeding rate than controls during the early stages of infection. In addition, feeding rates are lower in Imd mutants relative to the control larvae as the infection progresses. We further showed that Dilp2 and Dilp3 gene expression increases in Imd mutants compared to controls early in the infection, but their expression levels decrease at later times. These findings indicate that Imd signaling activity regulates the feeding rate and Dilp2 and Dilp3 expression in D. melanogaster larvae infected with H. gerrardi. Results from this study facilitate our understanding of the link between host innate immunity and sugar metabolism in the context of infectious diseases caused by parasitic nematodes.
摘要：
近年来在探索免疫代谢方面取得了重大进展，一个整合了维持组织和机体稳态所必需的两个过程的领域，免疫力和新陈代谢。线虫寄生虫杂种gerrardi，它的共生细菌不对称光带，果蝇果蝇构成了一个独特的系统，可以研究宿主对线虫-细菌复合物的免疫代谢反应的分子基础。在这项研究中,我们探索了两个主要的免疫信号通路的贡献，Toll和Imd,黑腹D.melanogaster幼虫在感染H.gerrardi线虫期间的糖代谢。我们用H.gerrardi线虫感染了Toll或Imd信号功能丧失突变幼虫，并评估了幼虫的生存能力，喂食率，和糖代谢。我们发现，当对H.gerrardi感染作出反应时，任何突变幼虫的存活能力或糖代谢产物水平都没有显着差异。然而,我们发现，在感染的早期阶段，Imd突变幼虫的摄食率高于对照。此外,随着感染的进行，相对于对照幼虫，Imd突变体的摄食率较低。我们进一步表明，与感染早期对照相比，Imd突变体中Dilp2和Dilp3基因表达增加，但它们的表达水平在以后降低。这些发现表明，Imd信号传导活性调节感染了H.gerrardi的黑腹D.幼虫的摄食率以及Dilp2和Dilp3的表达。这项研究的结果有助于我们了解寄生线虫引起的传染病中宿主先天免疫与糖代谢之间的联系。
