Tan Shumin, Russell David G
Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.
Immunol Rev. 2015 Mar;264(1):233-48. doi: 10.1111/imr.12254.
Much of the infection cycle of Mycobacterium tuberculosis (Mtb) is spent within its host cell, the macrophage. As a consequence of the chronic, enduring nature of the infection, this cell-cell interaction has become highly intimate, and the bacterium has evolved to detect, react to, and manipulate the evolving, immune-modulated phenotype of its host. In this review, we discuss the nature of the endosomal/lysosomal continuum, the characterization of the bacterium's transcriptional responses during the infection cycle, and the dominant environmental cues that shape this response. We also discuss how the metabolism of both cells is modulated by the infection and the impact that this has on the progression of the granuloma. Finally, we detail how these transcriptional responses can be exploited to construct reporter bacterial strains to probe the temporal and spatial environmental shifts experienced by Mtb during the course of experimental infections. These reporter strains provide new insights into the fitness of Mtb under immune- and drug-mediated pressure.
结核分枝杆菌（Mtb）感染周期的大部分时间是在其宿主细胞巨噬细胞内度过的。由于感染具有慢性、持续性的特点，这种细胞间相互作用变得非常密切，并且该细菌已经进化到能够检测、响应并操纵其宿主不断演变的、免疫调节的表型。在这篇综述中，我们讨论了内体/溶酶体连续体的性质、细菌在感染周期中的转录反应特征，以及塑造这种反应的主要环境线索。我们还讨论了感染如何调节两种细胞的代谢以及这对肉芽肿进展的影响。最后，我们详细阐述了如何利用这些转录反应构建报告细菌菌株，以探究Mtb在实验性感染过程中所经历的时空环境变化。这些报告菌株为Mtb在免疫和药物介导压力下的适应性提供了新的见解。
