Deffert Christine, Cachat Julien, Krause Karl-Heinz
Laboratory for Biological Fluids, University Hospitals and Faculty of Medicine of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, 14, Switzerland; Department of Pathology and Immunology, Medical Faculty and University of Geneva, 1211, Geneva, 4, Switzerland.
Cell Microbiol. 2014 Aug;16(8):1168-78. doi: 10.1111/cmi.12322. Epub 2014 Jul 7.
Infection of humans with Mycobacterium tuberculosis remains frequent and may still lead to death. After primary infection, the immune system is often able to control M. tuberculosis infection over a prolonged latency period, but a decrease in immune function (from HIV to immunosenescence) leads to active disease. Available vaccines against tuberculosis are restricted to BCG, a live vaccine with an attenuated strain of M. bovis. Immunodeficiency may not only be associated with an increased risk of tuberculosis, but also with local or disseminated BCG infection. Genetic deficiency in the reactive oxygen species (ROS)-producing phagocyte NADPH oxidase NOX2 is called chronic granulomatous disease (CGD). CGD is among the most common primary immune deficiencies. Here we review our knowledge on the importance of NOX2-derived ROS in mycobacterial infection. A literature review suggests that human CGD patient frequently have an increased susceptibility to BCG and to M. tuberculosis. In vitro studies and experiments with CGD mice are incomplete and yielded - at least in part - contradictory results. Thus, although observations in human CGD patients leave little doubt about the role of NOX2 in the control of mycobacteria, further studies will be necessary to unequivocally define and understand the role of ROS.
人类感染结核分枝杆菌的情况仍然很常见，并且仍可能导致死亡。初次感染后，免疫系统通常能够在较长的潜伏期内控制结核分枝杆菌感染，但免疫功能下降（从感染HIV到免疫衰老）会导致活动性疾病。现有的抗结核疫苗仅限于卡介苗，这是一种用减毒牛分枝杆菌菌株制成的活疫苗。免疫缺陷不仅可能与结核病风险增加有关，还可能与局部或播散性卡介苗感染有关。产生活性氧（ROS）的吞噬细胞NADPH氧化酶NOX2的基因缺陷被称为慢性肉芽肿病（CGD）。CGD是最常见的原发性免疫缺陷之一。在此，我们回顾关于NOX2衍生的ROS在分枝杆菌感染中的重要性的知识。文献综述表明，人类CGD患者通常对卡介苗和结核分枝杆菌的易感性增加。体外研究和对CGD小鼠的实验并不完整，并且至少部分产生了相互矛盾的结果。因此，尽管在人类CGD患者中的观察结果毋庸置疑地表明了NOX2在控制分枝杆菌中的作用，但仍需要进一步研究来明确界定和理解ROS的作用。
