Singapore Immunology Network, Singapore 138648.
EMBO Mol Med. 2009 Apr;1(1):19-29. doi: 10.1002/emmm.200900008.
Over thousands of years microbes and mammals have co-evolved, resulting in extraordinarily sophisticated molecular mechanisms permitting the organisms to survive together. Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human population, but in 90% of the cases without causing overt disease. Despite this, increasing incidence of Human Immunodeficiency Virus (HIV) infection and the emergence of drug-resistant strains means that tuberculosis is in fact an extremely serious emerging threat to global health. Decades of work have focused on the interaction of this pathogen with its established cellular host, the macrophage, but still novel therapeautics remain elusive. While the macrophage is clearly important, recent evidence suggests that understanding the role of dendritic cells, which are key regulators of immunity, may be a crucial step in identifying new means of controlling this disease. Novel technologies, in particular genome-wide transcriptome analyses, are advancing our ability to dissect the complex dynamic relationships between dendritic cells and mycobacteria, highlighting new areas for study that have not been previously explored.
数千年来,微生物和哺乳动物共同进化,形成了极其复杂的分子机制,使它们能够共生共存。结核分枝杆菌是成功共同进化的最佳范例之一,因为这种细菌已经感染了全球三分之一的人口,但在 90%的情况下不会引起明显的疾病。尽管如此,人类免疫缺陷病毒 (HIV) 感染的发病率不断上升和耐药菌株的出现意味着,结核病实际上是对全球健康的一个极其严重的新威胁。数十年来的研究工作集中在这种病原体与其既定的细胞宿主——巨噬细胞的相互作用上,但仍然难以找到新的治疗方法。虽然巨噬细胞显然很重要,但最近的证据表明,了解树突状细胞(调节免疫的关键细胞)的作用可能是确定控制这种疾病的新方法的关键步骤。新技术,特别是全基因组转录组分析,正在提高我们剖析树突状细胞和分枝杆菌之间复杂动态关系的能力,突出了以前未曾探索过的新研究领域。