Clark H Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, Alberta Children's Hospital Research Institute, University of Calgary, Alberta T2N 4N1, Canada.
Department of Biochemistry and Molecular Biology Calgary, University of Calgary, Alberta T2N 4N1, Canada.
G3 (Bethesda). 2022 Nov 4;12(11). doi: 10.1093/g3journal/jkac163.
When infected by intestinal pathogenic bacteria, animals initiate both local and systemic defence responses. These responses are required to reduce pathogen burden and also to alter host physiology and behavior to promote infection tolerance, and they are often mediated through alterations in host gene expression. Here, we have used transcriptome profiling to examine gene expression changes induced by enteric infection with the Gram-negative bacteria Pseudomonas entomophila in adult female Drosophila. We find that infection induces a strong upregulation of metabolic gene expression, including gut and fat body-enriched genes involved in lipid transport, lipolysis, and beta-oxidation, as well as glucose and amino acid metabolism genes. Furthermore, we find that the classic innate immune deficiency (Imd)/Relish/NF-KappaB pathway is not required for, and in some cases limits, these infection-mediated increases in metabolic gene expression. We also see that enteric infection with Pseudomonas entomophila downregulates the expression of many transcription factors and cell-cell signaling molecules, particularly those previously shown to be involved in gut-to-brain and neuronal signaling. Moreover, as with the metabolic genes, these changes occurred largely independent of the Imd pathway. Together, our study identifies many metabolic, signaling, and transcription factor gene expression changes that may contribute to organismal physiological and behavioral responses to enteric pathogen infection.
当动物感染肠道致病菌时,会启动局部和全身防御反应。这些反应需要减少病原体负担,还需要改变宿主的生理和行为以促进感染耐受,而这些反应通常是通过宿主基因表达的改变来介导的。在这里,我们使用转录组谱分析来研究革兰氏阴性菌假单胞菌属感染成年雌性果蝇时诱导的基因表达变化。我们发现感染强烈地上调了代谢基因的表达,包括与脂质转运、脂肪分解和β氧化以及葡萄糖和氨基酸代谢基因相关的肠道和脂肪体丰富的基因。此外,我们发现经典的先天免疫缺陷 (Imd)/Relish/NF-κB 途径对于这些感染介导的代谢基因表达的增加不是必需的,并且在某些情况下会限制这种增加。我们还发现,假单胞菌属感染肠道下调了许多转录因子和细胞间信号分子的表达,特别是那些先前被证明参与肠道到大脑和神经元信号传递的转录因子和细胞间信号分子。此外,与代谢基因一样,这些变化在很大程度上独立于 Imd 途径。总之,我们的研究确定了许多代谢、信号和转录因子基因表达的变化,这些变化可能有助于机体对肠道病原体感染的生理和行为反应。