Brucella melitensis triggers time-dependent modulation of a apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages
Brucella melitensis triggers time-dependent modulation of a apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages
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DOI：
10.1128/iai.01998-05
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发表时间：
2006-09-01
影响因子：
3.1
通讯作者：
Boyle, Stephen M.
中科院分区：
文献类型：
--
作者：
He, Yongqun;Reichow, Sherry;Boyle, Stephen M.
布鲁氏菌属是引起人类和其他动物布鲁氏菌病的兼性细胞内细菌。布鲁氏菌属被巨噬细胞摄取，巨噬细胞-布鲁氏菌相互作用的结果是建立慢性布鲁氏菌感染的基础。使用微阵列分析鼠巨噬细胞样 J774.A1 细胞系对强毒力布鲁氏菌菌株 16M 感染的转录反应。研究发现，巨噬细胞基因转录的最显着变化发生在感染后早期，并且整体巨噬细胞基因表达谱在感染后24至48小时内恢复正常。这些发现支持这样的观察结果：巨噬细胞在早期感染阶段杀死大多数布鲁氏菌细胞，但幸存的布鲁氏菌细胞能够在感染后期避免复制吞噬体内的巨噬细胞布鲁氏菌酸活性。感染后4小时，巨噬细胞中参与细胞生长、代谢和内源刺激反应的基因下调，而炎症反应（例如肿瘤坏死因子α和Toll样受体2）、补体系统、对外部刺激的反应和其他免疫反应上调。最活跃的布鲁氏菌酸活性可能发生在感染后 0 至 4 111 之间。感染后4小时，参与蛋白质合成和运输、电子转移、小分子转移以及许多其他线粒体功能的线粒体相关基因表达显着下调。尽管同时具有促细胞凋亡和抗细胞凋亡作用，但 B. melitensis 16M 似乎可以通过阻断细胞色素 c 的释放和线粒体中活性氧的产生来抑制巨噬细胞的细胞凋亡，从而防止 caspase 级联的激活。
Brucella spp. are facultative intracellular bacteria that cause brucellosis in humans and other animals. Brucella spp. are taken up by macrophages, and the outcome of the macrophage-Brucella interaction is a basis for establishment of a chronic Brucella infection. Microarrays were used to analyze the transcriptional response of the murine macrophage-like J774.A1 cell line to infection with virulent Brucella melitensis strain 16M. It was found that most significant changes in macrophage gene transcription happened early following infection, and global macrophage gene expression profiles returned to normal between 24 and 48 h postinfection. These findings support the observation that macrophages kill the majority of Brucella cells at the early infection stage, but the surviving Brucella cells are able to avoid macrophage brucellacidal activity inside replicative phagosomes at the later infection stage. At 4 h postinfection, macrophage genes involved in cell growth, metabolism, and responses to endogenous stimuli were down-regulated, while the inflammatory response (e.g., tumor necrosis factor alpha and Toll-like receptor 2), the complement system, the responses to external stimuli, and other immune responses were up-regulated. It is likely that the most active brucellacidal activity happened between 0 and 4 111 postinfection. Mitochondrion-associated gene expression, which is involved in protein synthesis and transport, electron transfer, and small-molecule transfer, and many other mitochondrial functions were significantly down-regulated at 4 h postinfection. Although there were both pro- and antiapoptosis effects, B. melitensis 16M appears to inhibit apoptosis of macrophages by blocking release of cytochrome c and production of reactive oxygen species in the mitochondria, thus preventing activation of caspase cascades.