Gene expression and TB pathogenesis in rhesus macaques: TR4, CD40, CD40L, FAS (CD95), and TNF are host genetic markers in peripheral blood mononuclear cells that are associated with severity of TB lesions.
Gene expression and TB pathogenesis in rhesus macaques: TR4, CD40, CD40L, FAS (CD95), and TNF are host genetic markers in peripheral blood mononuclear cells that are associated with severity of TB lesions.
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恒河猕猴中的基因表达和TB发病机理：TR4，CD40，CD40L，FAS（CD95）和TNF是与TB病变严重程度有关的外周血单核细胞中的宿主遗传标记。
DOI：
10.1016/j.meegid.2015.10.010
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发表时间：
2015-12
影响因子：
3.2
通讯作者：
Smith, David Glenn
中科院分区：
文献类型：
--
作者：
Roodgar, Morteza;Ross, Cody T.;Tarara, Ross;Lowenstine, Linda;Dandekar, Satya;Smith, David Glenn
恒河猴的结核病（TB）病理学病变与人类相似。在实验感染结核分枝杆菌的6只恒河猴的外周血单个核细胞（PBMC）中的几种宿主TB候选基因的表达水平在感染前和感染后的几个日期进行定量。肺中TB组织病理学的定量测量包括：肉芽肿计数、肉芽肿大小、肉芽肿性和非肉芽肿性病变的体积以及直接细菌负荷，被用作多水平贝叶斯回归模型的结果，其中宿主基因在不同日期的表达水平被用作预测因子。结果表明，PBMC中TR 4、CD 40、CD 40 L、FAS（CD 95）和TNF的表达水平与研究动物肺中TB组织病理学病变严重程度的定量测量相关。此外，IFNE在PBMC中的表达水平和研究动物的肺TB病变的严重程度之间没有可靠的关联被发现。总之，来自上述列出的宿主基因的PBMC表达谱可能是合适的生物标志物，用于概率诊断和/或预测恒河猴的TB严重程度。
Tuberculosis (TB) pathologic lesions in rhesus macaques resemble those in humans. The expression levels of several host TB candidate genes in the peripheral blood mononuclear cells (PBMCs) of six rhesus macaques experimentally infected with Mycobacterium tuberculosis were quantified pre-infection and at several dates post-infection. Quantitative measures of TB histopathology in the lungs including: granuloma count, granuloma size, volume of granulomatous and non-granulomatous lesions, and direct bacterial load, were used as the outcomes of a multi-level Bayesian regression model in which expression levels of host genes at various dates were used as predictors. The results indicate that the expression levels of TR4, CD40, CD40L, FAS (CD95) and TNF in PBMC were associated with quantitative measures of the severity of TB histopathologic lesions in the lungs of the study animals. Moreover, no reliable association between the expression levels of IFNE in PBMCs and the severity of TB lesions in the lungs of the study animals was found. In conclusion, PBMC expression profiles derived from the above-listed host genes might be appropriate biomarkers for probabilistic diagnosis and/or prognosis of TB severity in rhesus macaques.
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