Cliff Jacqueline M, Kaufmann Stefan H E, McShane Helen, van Helden Paul, O'Garra Anne
TB Centre and Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK.
Immunol Rev. 2015 Mar;264(1):88-102. doi: 10.1111/imr.12269.
The immune response upon infection with the pathogen Mycobacterium tuberculosis is poorly understood, hampering the discovery of new treatments and the improvements in diagnosis. In the last years, a blood transcriptional signature in tuberculosis has provided knowledge on the immune response occurring during active tuberculosis disease. This signature was absent in the majority of asymptomatic individuals who are latently infected with M. tuberculosis (referred to as latent). Using modular and pathway analyses of the complex data has shown, now in multiple studies, that the signature of active tuberculosis is dominated by overexpression of interferon-inducible genes (consisting of both type I and type II interferon signaling), myeloid genes, and inflammatory genes. There is also downregulation of genes encoding B and T-cell function. The blood signature of tuberculosis correlates with the extent of radiographic disease and is diminished upon effective treatment suggesting the possibility of new improved strategies to support diagnostic assays and methods for drug treatment monitoring. The signature suggested a previously under-appreciated role for type I interferons in development of active tuberculosis disease, and numerous mechanisms have now been uncovered to explain how type I interferon impedes the protective response to M. tuberculosis infection.
人们对感染病原体结核分枝杆菌后的免疫反应了解甚少，这阻碍了新疗法的发现和诊断方法的改进。在过去几年中，结核病的血液转录特征为活动性结核病期间发生的免疫反应提供了相关知识。在大多数潜伏感染结核分枝杆菌的无症状个体（称为潜伏感染者）中，这种特征并不存在。现在多项研究通过对复杂数据进行模块和通路分析表明，活动性结核病的特征主要表现为干扰素诱导基因（包括I型和II型干扰素信号传导）、髓系基因和炎症基因的过度表达。同时，编码B细胞和T细胞功能的基因也存在下调。结核病的血液特征与影像学疾病的严重程度相关，并且在有效治疗后会减弱，这表明有可能采用新的改进策略来支持诊断检测以及药物治疗监测方法。该特征表明I型干扰素在活动性结核病的发展中发挥了此前未被充分认识的作用，现在已经发现了许多机制来解释I型干扰素如何阻碍对结核分枝杆菌感染的保护性反应。
