Potential diagnostic value of the Peripheral blood mononuclear cell transcriptome from cattle with Bovine Tuberculosis

【作者】 房立春； 林伟东； 贾红； 高新桃； 隋修坤； 郭晓宇； 侯绍华； 姜一瞳； 朱良全； 朱鸿飞； 丁家波； 蒋琳； 鑫婷；

【机构】 中国农业科学院北京畜牧兽医研究所； 中国兽医药品监察所；

【摘要】 Bovine tuberculosis(bTB) is a chronic disease of cattle caused by Mycobacterium bovis.During early-stage infection,M.bovis-infected cattle shed mycobacteria through nasal secretions,which can be detected via nested-polymerase chain reaction(PCR) experiments.Little research has focused on immune responses in nested PCR-positive(bTB PCR-P) or nested PCR-negative(bTB PCR-N) M.bovis-infected cattle.Here,we investigated the transcriptomes of peripheral blood mononuclear cells(PBMCs),with or without stimulation by purified protein derivative of bovine tuberculin(PPD-B),among bTB PCR-P,bTB PCR-N,and healthy cattle using RNA-Seq.We also explored the potential value of PBMC transcripts as novel biomarkers for diagnosing bTB.Numerous differentially expressed genes were identified following pair-wise comparison of different groups,with or without PPD-B stimulation(adjusted p <0.05).Compared with healthy cattle,bTB PCR-P,and bTB PCR-N cattle shared 5 significantly dysregulated biological pathways,including Cytokine-cytokine receptor interaction,NF-kappa B signaling pathway,Hematopoietic cell lineage,Osteoclast differentiation and HTLV-I infection.Notably,dysregulated biological pathways of bTB PCR-P and bTB PCR-N cattle were associated with cell death and phagocytosis,respectively.Lymphotoxin alpha and interleukin-8 could potentially differentiate M.bovis-infected and healthy cattle upon stimulation with PPD-B,with area-under-the-curve(AUC) values of 0.9991 and0.9343,respectively.B celllymphoma2 and chitinase 3-like 1 might enable differentiation between bTB PCR-P and bTB PCR-N upon stimulation with PPD-B,with AUC values of 0.9100 and 0.8893,respectively.Thus,the PBMC transcriptome revealed the immune responses in M.bovis-infected cattle(bTB PCR-Pand bTB PCR-N) and may provide a novel sight in bTB diagnosis.更多还原

【Abstract】 Bovine tuberculosis(bTB) is a chronic disease of cattle caused by Mycobacterium bovis.During early-stage infection,M.bovis-infected cattle shed mycobacteria through nasal secretions,which can be detected via nested-polymerase chain reaction(PCR) experiments.Little research has focused on immune responses in nested PCR-positive(bTB PCR-P) or nested PCR-negative(bTB PCR-N) M.bovis-infected cattle.Here,we investigated the transcriptomes of peripheral blood mononuclear cells(PBMCs),with or without stimulation by purified protein derivative of bovine tuberculin(PPD-B),among bTB PCR-P,bTB PCR-N,and healthy cattle using RNA-Seq.We also explored the potential value of PBMC transcripts as novel biomarkers for diagnosing bTB.Numerous differentially expressed genes were identified following pair-wise comparison of different groups,with or without PPD-B stimulation(adjusted p <0.05).Compared with healthy cattle,bTB PCR-P,and bTB PCR-N cattle shared 5 significantly dysregulated biological pathways,including Cytokine-cytokine receptor interaction,NF-kappa B signaling pathway,Hematopoietic cell lineage,Osteoclast differentiation and HTLV-I infection.Notably,dysregulated biological pathways of bTB PCR-P and bTB PCR-N cattle were associated with cell death and phagocytosis,respectively.Lymphotoxin alpha and interleukin-8 could potentially differentiate M.bovis-infected and healthy cattle upon stimulation with PPD-B,with area-under-the-curve(AUC) values of 0.9991 and0.9343,respectively.B celllymphoma2 and chitinase 3-like 1 might enable differentiation between bTB PCR-P and bTB PCR-N upon stimulation with PPD-B,with AUC values of 0.9100 and 0.8893,respectively.Thus,the PBMC transcriptome revealed the immune responses in M.bovis-infected cattle(bTB PCR-Pand bTB PCR-N) and may provide a novel sight in bTB diagnosis.更多还原