Sessa R, Di Pietro M, Schiavoni G, Macone A, Maras B, Fontana M, Zagaglia C, Nicoletti M, Del Piano M, Morrone S
Department of Public Health Sciences, Sapienza University, Rome, Italy.
Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):659-68. doi: 10.1177/039463200902200311.
Chlamydia pneumoniae persistent infection has been implicated in the pathogenesis of several chronic inflammatory diseases including atherosclerosis, and we hypothesized that modulation of the apoptosis of macrophages and/or T cells by C. pneumoniae infection may contribute to the development of such diseases. We therefore evaluated apoptosis, cytokine response, and redox status in human primary T cells and macrophages infected with C. pneumoniae. In addition, co-cultures of T cells and macrophages infected with C. pneumoniae were also carried out. Apoptosis, and levels of glutathione (GSH), glutathione disulfide (GSSG), and tumour necrosis factor (TNF)-alpha were measured by flow cytometry, high performance liquid chromatography and enzyme-linked immunosorbent assay. C. pneumoniae induced apoptosis in T cells as well as in co-cultures of T cells and infected macrophages by marked decrease in GSH/GSSG ratio and increased production of TNF-alpha, respectively. The results demonstrate that interaction of C. pneumoniae with T cells and/or macrophages characterized by interference with redox status, and secretion of tumour necrosis factor-alpha culminates in the induction of T cell apoptosis and survival of infected macrophages. In conclusion, the inappropriate T cell response against C. pneumoniae and survival of infected macrophages could explain the persistence of this intracellular obligate pathogen in the host-organism; it may contribute to the development of chronic inflammatory diseases, although further studies are needed to clarify such a complex mechanism.
肺炎衣原体持续感染与包括动脉粥样硬化在内的多种慢性炎症性疾病的发病机制有关，我们推测肺炎衣原体感染对巨噬细胞和/或T细胞凋亡的调节可能促成此类疾病的发展。因此，我们评估了感染肺炎衣原体的人原代T细胞和巨噬细胞中的凋亡、细胞因子反应及氧化还原状态。此外，还进行了感染肺炎衣原体的T细胞与巨噬细胞的共培养。通过流式细胞术、高效液相色谱法和酶联免疫吸附测定法测量凋亡以及谷胱甘肽（GSH）、二硫化谷胱甘肽（GSSG）和肿瘤坏死因子（TNF）-α的水平。肺炎衣原体分别通过显著降低GSH/GSSG比值和增加TNF-α的产生，诱导T细胞以及T细胞与感染巨噬细胞共培养体系中的凋亡。结果表明，肺炎衣原体与T细胞和/或巨噬细胞的相互作用表现为氧化还原状态受到干扰以及肿瘤坏死因子-α的分泌，最终导致T细胞凋亡和感染巨噬细胞的存活。总之，针对肺炎衣原体的不适当T细胞反应以及感染巨噬细胞的存活可以解释这种细胞内专性病原体在宿主体内的持续存在；这可能促成慢性炎症性疾病的发展，不过还需要进一步研究来阐明这种复杂机制。
