Rohde Kyle H, Abramovitch Robert B, Russell David G
Cornell University, College of Veterinary Medicine, Department of Microbiology and Immunology, Ithaca, NY 14853, USA.
Cell Host Microbe. 2007 Nov 15;2(5):352-64. doi: 10.1016/j.chom.2007.09.006.
A central feature of Mycobacterium tuberculosis (Mtb) pathogenesis is the ability of Mtb to survive within macrophages (MØ). Despite its critical importance, our appreciation of the interplay between these two cells remains superficial. We employed microarrays to conduct a stepwise dissection of Mtb-MØ interaction during the invasion of resting bone marrow MØ. Contrary to many bacterial pathogens, engagement by MØ receptors without internalization did not alter Mtb gene expression. Subsequently, a high-resolution profile of Mtb invasion-linked gene expression was generated by assaying the Mtb transcriptome at 20 min intervals up to 2 hr postinfection. Transcriptional responses were detected within minutes of phagocytosis, including gene subsets with distinct temporal profiles. Pharmacological manipulation of phagosomal pH and in vitro acid stress studies revealed that vacuole acidification is an important trigger for differential gene expression. Finally, there are marked species-specific differences in the response of Mtb and M. bovis BCG to intraphagosomal cues.
结核分枝杆菌（Mtb）致病机制的一个核心特征是Mtb在巨噬细胞（MØ）内生存的能力。尽管其至关重要，但我们对这两种细胞之间相互作用的理解仍很肤浅。我们利用微阵列对静息骨髓MØ侵袭过程中Mtb-MØ相互作用进行了逐步剖析。与许多细菌病原体不同，MØ受体的结合而不发生内化并不会改变Mtb的基因表达。随后，通过在感染后2小时内每隔20分钟检测Mtb转录组，生成了Mtb侵袭相关基因表达的高分辨率图谱。吞噬作用几分钟内就检测到了转录反应，包括具有不同时间特征的基因子集。对吞噬体pH的药理学操作和体外酸应激研究表明，液泡酸化是差异基因表达的重要触发因素。最后，Mtb和牛分枝杆菌卡介苗（M. bovis BCG）对吞噬体内信号的反应存在明显的物种特异性差异。
