PDF(Pubmed)
Abstract：
Paratuberculosis or Johne\'s disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (CCL20, CCL5, CD40, CSF2, CXCL8, EIF2AK2, FOS, IL10, IL17A, IL1A, IL1B, IRF1, MX2, NFKB1, NFKBIA, PTGS2, SOCS3, TLR4, TNF, TNFAIP3, and VCAM1) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle.
摘要：
副结核病或约翰氏病（JD），由鸟分枝杆菌亚种引起的慢性肉芽肿性胃肠炎。副结核病（MAP），造成巨大的经济损失，降低了全球奶牛群的动物福利。目前,对奶牛MAP感染免疫反应的分子机制和生物学功能尚不清楚。我们的目的是整合转录组学谱和竞争性内源性RNA（ceRNA）网络分析，以鉴定参与乳牛MAP感染的外周血单核细胞（PBMC）分子调控的关键信使RNA（mRNA）和调控RNA。总的来说,28个lncRNAs,42个miRNA,通过整合基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析鉴定了370个mRNA。在这方面,我们鉴定了21个hub基因(CCL20、CCL5、CD40、CSF2、CXCL8、EIF2AK2、FOS、IL10,IL17A,IL1A,IL1B,IRF1,MX2,NFKB1,NFKBIA,PTGS2,SOCS3,TLR4,TNF,TNFAIP3和VCAM1）参与MAP感染。此外，具有八个lncRNAs的八个候选子网，29个miRNA,并通过聚类分析检测到237个mRNA，而GO富集分析鉴定的RNA显示510、22和11显著富集与生物过程中MAP感染相关的GO术语，分子功能，和细胞组件类别，分别。富集的与MAP感染相关的主要代谢信号通路包括免疫系统过程,防御反应,对细胞因子的反应，白细胞迁移,调节T细胞活化，对细菌的防御反应，NOD样受体,B细胞受体，TNF,NF-κB,IL-17和T细胞受体信号通路。来自MAP阳性和MAP阴性样品组的转录组谱的贡献以及在JD致病性强度中潜在的表型差异的ceRNA调节网络提供了与奶牛对MAP感染的免疫系统反应相关的分子机制的新见解。
