Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, Animal Genetic Engineering Key Lab of Haikou, School of Animal Science and Technology, Hainan University, Haikou, Hainan, China.
Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, Animal Genetic Engineering Key Lab of Haikou, School of Animal Science and Technology, Hainan University, Haikou, Hainan, China.
Microb Pathog. 2023 Oct;183:106212. doi: 10.1016/j.micpath.2023.106212. Epub 2023 Jun 21.
Pasteurella multocida (P. multocida) is a highly infectious, zoonotic pathogen. Outer membrane protein A (OmpA) is an important virulence component of the outer membrane of P. multocida. OmpA mediates bacterial biofilm formation, eukaryotic cell infection, and immunomodulation. It is unclear how OmpA affects the host immune response. We estimated the role of OmpA in the pathogenesis of P. multocida by investigating the effect of OmpA on the immune cell transcriptome. Changes in the transcriptome of rat alveolar macrophages (NR8383) upon overexpression of P. multocida OmpA were demonstrated. A model cell line for stable transcription of OmpA was constructed by infecting NR8383 cells with OmpA-expressing lentivirus. RNA was extracted from cells and sequenced on an Illumina HiSeq platform. Key gene analysis of genes in the RNA-seq dataset were performed using various bioinformatics methods, such as gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, and Protein-Protein Interaction Analysis. Our findings revealed 1340 differentially expressed genes. Immune-related pathways that were significantly altered in rat alveolar macrophages under the effect of OmpA included focal adhesion, extracellular matrix and vascular endothelial growth factor signaling pathways, antigen processing and presentation, nucleotide oligomerization domain-like receptor and Toll-like receptor signaling pathways, and cytokine-cytokine receptor interaction. The key genes screened were Vegfa, Igf2r, Fabp5, P2rx1, C5ar1, Nedd4l, Gas6, Cxcl1, Pf4, Pdgfb, Thbs1, Col7a1, Vwf, Ccl9, and Arg1. Data of associated pathways and altered gene expression indicated that OmpA might cause the conversion of rat alveolar macrophages to M2-like. The related pathways and key genes can serve as a reference for OmpA of P. multitocida and host interaction mechanism studies.
多杀巴斯德菌（Pasteurella multocida，P. multocida）是一种高度传染性的人畜共患病病原体。外膜蛋白 A（Outer membrane protein A，OmpA）是多杀巴斯德菌外膜的重要毒力成分。OmpA 介导细菌生物膜形成、真核细胞感染和免疫调节。目前尚不清楚 OmpA 如何影响宿主免疫反应。我们通过研究 OmpA 对免疫细胞转录组的影响，来估计 OmpA 在多杀巴斯德菌发病机制中的作用。结果显示，过表达多杀巴斯德菌 OmpA 可改变大鼠肺泡巨噬细胞（NR8383）的转录组。通过感染表达 OmpA 的慢病毒构建了稳定转录 OmpA 的模型细胞系。从细胞中提取 RNA，并在 Illumina HiSeq 平台上进行测序。使用各种生物信息学方法对 RNA-seq 数据集的基因进行了关键基因分析，包括基因本体富集分析、京都基因与基因组百科全书富集分析、基因集富集分析和蛋白质-蛋白质相互作用分析。我们的研究结果显示，有 1340 个差异表达基因。在 OmpA 作用下，大鼠肺泡巨噬细胞中显著改变的免疫相关途径包括粘着斑、细胞外基质和血管内皮生长因子信号通路、抗原加工和呈递、核苷酸寡聚化结构域样受体和 Toll 样受体信号通路以及细胞因子-细胞因子受体相互作用。筛选出的关键基因包括 Vegfa、Igf2r、Fabp5、P2rx1、C5ar1、Nedd4l、Gas6、Cxcl1、Pf4、Pdgfb、Thbs1、Col7a1、Vwf、Ccl9 和 Arg1。相关途径和改变的基因表达数据表明，OmpA 可能导致大鼠肺泡巨噬细胞向 M2 样转化。相关途径和关键基因可以作为多杀巴斯德菌 OmpA 与宿主相互作用机制研究的参考。
