Department of Engineering and Applied Biology, College of Life Science, Sichuan Agricultural University, Ya'an, 625014, Sichuan, PR China.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, PR China.
Fish Shellfish Immunol. 2020 Feb;97:235-247. doi: 10.1016/j.fsi.2019.12.050. Epub 2019 Dec 19.
Lipopolysaccharide (LPS) is a classical pathogen-associated molecular pattern that can trigger strong inflammatory response mainly by TLR4-mediated signaling pathway in mammals, but the molecular mechanism of anti-LPS immunity is unclear in teleost fishes. In this study, we analyzed the gene expression features based on transcriptome analysis in Schizothorax prenanti (S. prenanti), after stimulation with two sources of LPS from Aeromonas hydrophila and Escherichia coli (Ah. LPS and Ecoli. LPS). 921 different expression genes (DEGs) after Ah. LPS stimulation and 975 DEGs after Ecoli.LPS stimulation were acquired, but only 706 and 750 DEGs were successfully annotated into the databases, respectively. Both of two groups of DGEs were significantly enriched into immune-related pathways by KEGG enrichment analysis, such as "Toll-like receptor signaling pathway", "Cytokine-cytokine receptor interaction" and "JAK-STAT signaling pathway". The annotated DEGs from Ah. LPS and Ecoli. LPS stimulation shared 470 DEGs, including 88 immune-related DEGs (IRGs) identified mainly by KEGG enrichment to immune-related signaling pathways. Among the shared IRGs, four pattern-recognition genes (TLR5, TLR25, PTX3 and C1q) were induced with high expression foldchange, and IFN-γ and relative genes also showed higher expression levels than control. Meanwhile, inflammatory signals were highlighted by upregulating the expression of inflammatory cytokines (IL-1β, IL-10 and IL-8). Moreover, some non-shared IRGs (including TLR2 and TLR4) were identified, suggesting that different sources of LPS own different potentials for the induction of immune gene expression. In conclusion, TLR5, TLR25, PTX3 and C1q may function as the sensing molecules to catch the invasion signal of LPS. The anti-LPS immune response may be involved into TLR25/TLR5-mediated inflammatory signals that regulate subsequently the activation of PTX3/C1q-modulated complement pathway upon the induction of PTX3 expression, and the crosstalk between IFN-γ and TLR signaling pathways in teleost fishes. This study will contribute to further explore the molecular mechanism of LPS-induced immunity in teleost fishes.
脂多糖（LPS）是一种经典的病原体相关分子模式，可通过哺乳动物 TLR4 介导的信号通路引发强烈的炎症反应，但在鱼类中抗 LPS 免疫的分子机制尚不清楚。在这项研究中，我们基于转录组分析，分析了齐口裂腹鱼（Schizothorax prenanti）在受到两种来自嗜水气单胞菌和大肠杆菌的 LPS（Ah. LPS 和 Ecoli. LPS）刺激后的基因表达特征。在 Ah. LPS 刺激后获得了 921 个差异表达基因（DEGs），在 Ecoli. LPS 刺激后获得了 975 个 DEGs，但只有 706 和 750 个 DEGs成功注释到数据库中。两组 DEGs 均通过 KEGG 富集分析显著富集到免疫相关途径，如“Toll 样受体信号通路”、“细胞因子-细胞因子受体相互作用”和“JAK-STAT 信号通路”。来自 Ah. LPS 和 Ecoli. LPS 刺激的注释 DEGs 共享 470 个 DEGs，其中包括通过 KEGG 富集到免疫相关信号通路的 88 个免疫相关 DEGs（IRGs）。在共享的 IRGs 中，4 个模式识别基因（TLR5、TLR25、PTX3 和 C1q）的诱导表达具有较高的折叠变化，IFN-γ 和相对基因的表达水平也高于对照。同时，通过上调炎症细胞因子（IL-1β、IL-10 和 IL-8）的表达，突出了炎症信号。此外，还鉴定了一些非共享的 IRGs（包括 TLR2 和 TLR4），这表明不同来源的 LPS 对免疫基因表达的诱导具有不同的潜力。综上所述，TLR5、TLR25、PTX3 和 C1q 可能作为感应分子，捕捉 LPS 入侵信号。抗 LPS 免疫反应可能涉及 TLR25/TLR5 介导的炎症信号，随后调节 PTX3 表达后 PTX3/C1q 调节补体途径的激活，以及 IFN-γ 和 TLR 信号通路在鱼类中的串扰。本研究将有助于进一步探讨鱼类 LPS 诱导免疫的分子机制。
