Seattle Children's Research Institute, Seattle, Washington, USA.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich,Switzerland.
J Infect Dis. 2022 May 16;225(10):1832-1840. doi: 10.1093/infdis/jiab130.
Previous studies have identified whole-blood transcriptional risk and disease signatures for tuberculosis; however, several lines of evidence suggest that these signatures primarily reflect bacterial burden, which increases before symptomatic disease. We found that the peripheral blood transcriptome of mice with contained Mycobacterium tuberculosis infection (CMTI) has striking similarities to that of humans with active tuberculosis and that a signature derived from these mice predicts human disease with accuracy comparable to that of signatures derived directly from humans. A set of genes associated with immune defense are up-regulated in mice with CMTI but not in humans with active tuberculosis, suggesting that their up-regulation is associated with bacterial containment. A signature comprising these genes predicts both protection from tuberculosis disease and successful treatment at early time points where current signatures are not predictive. These results suggest that detailed study of the CMTI model may enable identification of biomarkers for human tuberculosis.
先前的研究已经确定了全血转录风险和结核病的疾病特征；然而，有几条证据表明，这些特征主要反映了细菌负担，在出现症状性疾病之前会增加。我们发现，感染有结核分枝杆菌的小鼠的外周血转录组与活动性结核病患者的人类转录组有惊人的相似之处，并且从这些小鼠中提取的特征可以准确预测人类疾病，其准确性与直接从人类中提取的特征相当。一组与免疫防御相关的基因在感染有结核分枝杆菌的小鼠中上调，但在活动性结核病患者中没有上调，这表明它们的上调与细菌控制有关。由这些基因组成的特征预测了在当前特征没有预测性的早期时间点，既可以预防结核病，又可以成功治疗。这些结果表明，对 CMTI 模型的详细研究可能能够鉴定人类结核病的生物标志物。
