Prospective Discrimination of Controllers From Progressors Early After Low-Dose Mycobacterium tuberculosis Infection of Cynomolgus Macaques using Blood RNA Signatures.
Prospective Discrimination of Controllers From Progressors Early After Low-Dose Mycobacterium tuberculosis Infection of Cynomolgus Macaques using Blood RNA Signatures.
复制标题
使用血液 RNA 特征对食蟹猴进行低剂量结核分枝杆菌感染后早期的控制者与进展者的前瞻性区分。
DOI：
10.1093/infdis/jiy006
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Zak,DanielE
中科院分区：
文献类型：
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作者：
Thompson,EthanG;Shankar,Smitha;Gideon,HannahP;Braun,Jackie;Valvo,Joe;Skinner,JasonA;Aderem,Alan;Flynn,JoAnneL;Lin,PhilanaLing;Zak,DanielE
低剂量结核分枝杆菌感染的食蟹猴模型概括了人类结核病病理学的临床方面，但尚不清楚这两个系统是否足够相似，以至于基于宿主的结核病特征可以在跨物种之间进行预测。通过盲目预测，我们证明，包含人类结核病风险特征的基因子集可以同时预测人类和猕猴，并在感染后 3-6 周前瞻性地区分进展者和对照动物。进一步分析产生了涉及 PRDX2 的 3 基因特征，该特征可预测猕猴在攻击后 10 天的结核病进展，这表明定义对结核分枝杆菌的保护性反应的新途径。结核。
The cynomolgus macaque model of low-doseMycobacterium tuberculosisinfection recapitulates clinical aspects of human tuberculosis pathology, but it is unknown whether the 2 systems are sufficiently similar that host-based signatures of tuberculosis will be predictive across species. By blind prediction, we demonstrate that a subset of genes comprising a human signature for tuberculosis risk is simultaneously predictive in humans and macaques and prospectively discriminates progressor from controller animals 3–6 weeks after infection. Further analysis yielded a 3-gene signature involvingPRDX2that predicts tuberculosis progression in macaques 10 days after challenge, suggesting novel pathways that define protective responses toM. tuberculosis.