Transcriptional profile of Mycobacterium tuberculosis replicating in type II alveolar epithelial cells.
Transcriptional profile of Mycobacterium tuberculosis replicating in type II alveolar epithelial cells.
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DOI：
10.1371/journal.pone.0123745
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Laal S
中科院分区：
文献类型：
--
作者：
Ryndak MB;Singh KK;Peng Z;Laal S
结核分枝杆菌（M.肺结核）感染是由吸入肺泡的少量杆菌引起的。对气溶胶感染小鼠肺部的研究为M.在感染后的前2-3周期间，肺结核在肺泡中的非迁移、非抗原呈递细胞中。肺泡由II型和I型肺泡上皮细胞（AEC）排列，其数量超过肺泡巨噬细胞数百倍。M. tb DNA和活M.结核病已在来自结核病流行地区的潜伏感染受试者的尸检组织中的肾、肝和脾的AEC和其他非巨噬细胞中得到证实，表明在原发感染期间全身性细菌传播。M. tb也已被证明在A549细胞（II型AEC系）中快速复制并获得对内皮细胞的增加的侵袭力。总之，这些结果表明，AEC可以提供一个重要的生态位的细菌扩张和发展的表型，促进传播过程中的主要感染。在目前的研究中，我们比较了M。tb在A549细胞中的细胞内复制与M.通过微阵列分析，在实验室肉汤中复制结核。在细胞内驻留期间显著上调的基因与活跃、复制、代谢和有氧状态一致，色氨酸合成和增加毒力的基因（ESAT-6和ESAT-6样基因，esxH、esxJ、esxK、esxP和esxW）也是如此。相反，观察到DevR（DosR）调节子和几个缺氧诱导基因的显著下调。应激反应基因要么没有差异表达，要么下调，但热休克反应和低pH诱导的基因除外。tb转录组强有力地表明AEC可以提供M.结核病可在引发适应性免疫反应之前急剧扩大并从肺传播。
Mycobacterium tuberculosis (M. tb) infection is initiated by the few bacilli inhaled into the alveolus. Studies in lungs of aerosol-infected mice provided evidence for extensive replication of M. tb in non-migrating, non-antigen-presenting cells in the alveoli during the first 2–3 weeks post-infection. Alveoli are lined by type II and type I alveolar epithelial cells (AEC) which outnumber alveolar macrophages by several hundred-fold. M. tb DNA and viable M. tb have been demonstrated in AEC and other non-macrophage cells of the kidney, liver, and spleen in autopsied tissues from latently-infected subjects from TB-endemic regions indicating systemic bacterial dissemination during primary infection. M. tb have also been demonstrated to replicate rapidly in A549 cells (type II AEC line) and acquire increased invasiveness for endothelial cells. Together, these results suggest that AEC could provide an important niche for bacterial expansion and development of a phenotype that promotes dissemination during primary infection. In the current studies, we have compared the transcriptional profile of M. tb replicating intracellularly in A549 cells to that of M. tb replicating in laboratory broth, by microarray analysis. Genes significantly upregulated during intracellular residence were consistent with an active, replicative, metabolic, and aerobic state, as were genes for tryptophan synthesis and for increased virulence (ESAT-6, and ESAT-6-like genes, esxH, esxJ, esxK, esxP, and esxW). In contrast, significant downregulation of the DevR (DosR) regulon and several hypoxia-induced genes was observed. Stress response genes were either not differentially expressed or were downregulated with the exception of the heat shock response and those induced by low pH. The intra-type II AEC M. tb transcriptome strongly suggests that AEC could provide a safe haven in which M. tb can expand dramatically and disseminate from the lung prior to the elicitation of adaptive immune responses.
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影响因子：
5.2
作者：
Bukka, Archana;Price, Christopher T. D.;Graham, James E.
通讯作者：
Graham, James E.
DOI：
10.1385/0-89603-471-2:285
发表时间：
1998-01-01
期刊：
MYCOBACTERIA PROTOCOLS
影响因子：
--
作者：
Butcher, PD;Mangan, JA;Monahan, IM
通讯作者：
Monahan, IM
影响因子：
3.1
作者：
Chackerian, AA;Alt, JM;Behar, SM
通讯作者：
Behar, SM
影响因子：
3.1
作者：
Birkness, KA;Deslauriers, M;Quinn, FD
通讯作者：
Quinn, FD
影响因子：
3.5
作者：
Chung, Hwan-Suck;Kim, Youngeun;Bae, Hyunsu
通讯作者：
Bae, Hyunsu