Schrader Sina, Klos Andreas, Hess Simone, Zeidler Henning, Kuipers Jens G, Rihl Markus
Division of Rheumatology, Hannover Medical School (MHH), Carl-Neuberg-Str, 1, 30625 Hannover, Germany.
Arthritis Res Ther. 2007;9(3):R54. doi: 10.1186/ar2209.
The aim of this study was to perform a comprehensive gene expression analysis of cytokines, chemokines, and their receptors in Chlamydia trachomatis-infected human monocytes in order to elucidate molecular aspects of their involvement in the host response. Peripheral blood mononuclear cells from three healthy donors were separated and infected with C. trachomatis elementary bodies serovar K (UW/31/Cx) at a multiplicity of infection of 5:1. Three time points of infection were studied by gene expression analysis using microarray: 4 hours (active infection), 1 day (transition), and 7 days (persistent infection). Expression levels of selected genes were confirmed by quantitative real-time reverse transcription-polymerase chain reaction. Transcripts encoding 10 cytokines, chemokines, and receptors were found to be upregulated exclusively in the early, active phase of the infection as compared to four genes in the late, persistent state of the infection. Apart from receptors, both the level and the number of transcripts encoding inflammatory products decreased with ongoing infection. Four genes (interferon-gamma, macrophage inflammatory protein [MIP]-1-alpha, MIP-1-beta, and interleukin-2 receptor-gamma) were constantly expressed over a period of 7 days. The current study provides data on the induction of mRNA encoding cytokines, chemokines, and their receptors in C. trachomatis-infected human monocytes. This pro-inflammatory gene expression profile of the monocytic host cell showed several differences between active and persistent chlamydial infections.
本研究的目的是对沙眼衣原体感染的人单核细胞中的细胞因子、趋化因子及其受体进行全面的基因表达分析,以阐明它们参与宿主反应的分子机制。从三名健康供体分离出外周血单核细胞,并用血清型K(UW/31/Cx)的沙眼衣原体原体以5:1的感染复数进行感染。通过使用微阵列的基因表达分析研究了三个感染时间点:4小时(活跃感染)、1天(转变期)和7天(持续感染)。通过定量实时逆转录-聚合酶链反应确认了所选基因的表达水平。与感染后期持续状态下的四个基因相比,发现编码10种细胞因子、趋化因子和受体的转录本仅在感染的早期活跃阶段上调。除了受体外,随着感染的持续,编码炎症产物的转录本水平和数量均下降。四个基因(干扰素-γ、巨噬细胞炎性蛋白[MIP]-1-α、MIP-1-β和白细胞介素-2受体-γ)在7天内持续表达。本研究提供了沙眼衣原体感染的人单核细胞中编码细胞因子、趋化因子及其受体的mRNA诱导的数据。单核细胞宿主细胞的这种促炎基因表达谱在活跃和持续的衣原体感染之间显示出一些差异。