Host cell responses to Chlamydia pneumoniae in gamma interferon-induced persistence overlap those of productive infection and are linked to genes involved in apoptosis, cell cycle, and metabolism
Host cell responses to Chlamydia pneumoniae in gamma interferon-induced persistence overlap those of productive infection and are linked to genes involved in apoptosis, cell cycle, and metabolism
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DOI：
10.1128/iai.01045-06
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Klos, Andreas
中科院分区：
文献类型：
--
作者：
Eickhoff, Meike;Thalmann, Jessica;Klos, Andreas
呼吸道病原体肺炎衣原体（Chlamydia（Chlamydophila）pneumoniae）与慢性疾病相关，包括动脉粥样硬化和巨细胞动脉炎，其伴随着这些专性细胞内细菌在血管中的发生。在那里，肺炎衣原体似乎以持续状态存在。持续性的特征是细菌代谢和形态发生改变，以及衣原体发育的可逆停滞。在细胞培养中，这种持续状态可以由γ干扰素（IFN-γ）诱导。为了阐明衣原体和它们的宿主细胞之间的这种长期相互作用，对上皮HeLa细胞进行微阵列筛选。转录持续（和生产）感染的细胞进行了比较，与模拟感染的细胞。66个宿主细胞基因在IFN-γ诱导的持久性的24小时和/或96小时的调节。随后，一组17个人类宿主细胞基因相关的凋亡，细胞周期，或代谢被确定为永久上调或下调实时PCR。这些衣原体依赖的宿主细胞反应中的一些在利福平的存在下减少或甚至不存在。然而，其他表达模式没有改变细菌RNA聚合酶的抑制，这表明两种不同的宿主细胞激活模式。因此，在IFN-γ模型中，持续存在的细菌引起编码功能重要蛋白质的基因表达的长期变化。它们可能是治疗持续性丙型肝炎的潜在药物靶点。肺炎感染。
The respiratory pathogen Chlamydia (Chlamydophila) pneumoniae is associated with chronic diseases, including atherosclerosis and giant-cell arteritis, which are accompanied by the occurrence of these obligate intracellular bacteria in blood vessels. There, C pneumoniae seems to be present in a persistent state. Persistence is characterized by modified bacterial metabolism and morphology, as well as a reversible arrest of chlamydial development. In cell culture, this persistent state can be induced by gamma interferon (IFN-gamma). To elucidate this long-term interaction between chlamydiae and their host cells, microarray screening on epithelial HeLa cells was performed. Transcription of persistently (and productively) infected cells was compared with that of mock-infected cells. Sixty-six host cell genes were regulated at 24 h and/or 96 h of IFN-gamma-induced persistence. Subsequently, a set of 17 human host cell genes related to apoptosis, cell cycle, or metabolism was identified as permanently up- or down-regulated by real-time PCR. Some of these chlamydia-dependent host cell responses were diminished or even absent in the presence of rifampin. However, other expression patterns were not altered by the inhibition of bacterial RNA polymerase, suggesting two different modes of host cell activation. Thus, in the IFN-gamma model, the persisting bacteria cause long-lasting changes in the expression of genes coding for functionally important proteins. They might be potential drug targets for the treatment of persistent C. pneumoniae infections.