Mycobacterium tuberculosis invasion of macrophages:: Linking bacterial gene expression to environmental cues
Mycobacterium tuberculosis invasion of macrophages:: Linking bacterial gene expression to environmental cues
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DOI：
10.1016/j.chom.2007.09.006
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发表时间：
2007-11-01
影响因子：
30.3
通讯作者：
Russell, David G.
中科院分区：
文献类型：
--
作者：
Rohde, Kyle H.;Abramovitch, Robert B.;Russell, David G.
结核分枝杆菌(Mtb)致病机制的一个主要特征是Mtb在巨噬细胞内存活的能力(M空集)。尽管它至关重要，但我们对这两个细胞之间的相互作用的认识仍然很肤浅。我们利用微阵列对静息骨髓M空集侵袭过程中Mtb-M空集相互作用进行了逐步剖析。与许多细菌病原体相反，没有内化的M空集受体结合并不改变Mtb基因的表达。随后，通过每隔20分钟至感染后2小时对结核分枝杆菌转录组进行分析，生成了结核分枝杆菌侵袭相关基因表达的高分辨率图谱。在吞噬后的几分钟内检测到转录反应，包括具有不同时间分布的基因亚群。对吞噬体pH的药理调控和体外酸胁迫研究表明，空泡酸化是差异基因表达的重要触发因素。最后，结核分枝杆菌和卡介苗对吞噬体内线索的反应存在明显的物种特异性差异。
A central feature of Mycobacterium tuberculosis (Mtb) pathogenesis is the ability of Mtb to survive within macrophages (M empty set). 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-M empty set interaction during the invasion of resting bone marrow M empty set. Contrary to many bacterial pathogens, engagement by M empty set 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.