Chlamydia pneumoniae persistent infection and its mechanism

目前的研究表明，专性细胞内细菌肺炎衣原体（嗜衣原体）不仅与呼吸系统疾病有关，而且与动脉粥样硬化等慢性疾病有关。C.冠状动脉粥样硬化斑块和心血管疾病患者外周血中肺炎克雷伯氏菌DNA或抗原的存在，增强了其参与动脉粥样硬化发病的可能性。此外，一些研究表明，可行的C。用培养和RT-PCR方法均可在高龄冠心病患者的动脉粥样硬化斑块中检测到肺炎克雷伯氏菌。我们最近的研究也表明，可行的C。在从健康供体获得的外周血单核细胞（PBMC）中容易检测到肺炎链球菌，表明血流中活细菌的存在可能是动脉粥样硬化发展的危险因素。C.肺炎优先感染呼吸道 ...更多信息 以及巨噬细胞。另一方面，我们前期的研究表明淋巴细胞是另一种允许C.肺炎感染具有持续性。由于淋巴细胞是动脉粥样硬化发展过程中除巨噬细胞外的主要免疫细胞类型，因此淋巴细胞与该病原体之间的相互作用可能有助于与C相关的慢性炎症性疾病的发病机制。肺炎。我们首先试图评估非肥胖糖尿病（NOD）小鼠糖尿病的发生与C。从肺到外周血。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）技术，对C. pneumoniae 16 S rRNA，在多次鼻内接种后，糖尿病NOD小鼠和ICR小鼠肺组织中细菌检出率分别为38.5%和40%，而非糖尿病NOD小鼠（糖尿病前期NOD小鼠和非糖尿病退休NOD小鼠）肺组织中细菌检出率很低（4.8%），仅在糖尿病NOD小鼠氢化可的松培养的外周血单个核细胞（PBMCs）中检出细菌（53.8%）。异硫氰酸荧光素标记的抗衣原体单克隆抗体的免疫染色结果也显示肺中存在细菌抗原，并且通过RT-PCR判断PBMCs为阳性。结果表明，NOD小鼠糖尿病的发生是促进C.从肺到外周血。其次，我们研究了C.肺炎感染。C.肺炎感染。C. pneumoniae临床分离物也引起感染细胞的这两种表达的改变。与此相反，C.沙眼衣原体感染对Molt-4细胞的两种表达均无影响。热灭活细菌和HEp-2裂解物作为模拟物未引起淋巴细胞CD 3表达的任何改变。加入NS-398（考克斯-2抑制剂）或AH-23848（EP 4前列腺素受体拮抗剂）后，感染细胞的CD 3表达改变消失。竞争性ELISA也证实了感染细胞培养上清中前列腺素E_2（PGE_2）的产生增加。C. pneumoniae感染PBMC中富集的淋巴细胞也可引起CD 3表达的改变。pneumoniae感染人淋巴细胞后，通过PGE_2的产生，诱导CD 3表达的改变。由于CD 3分子在抗原清除后的信号转导中起主要作用，这种改变可能与肺炎衣原体持续感染淋巴细胞有关。此外，我们还发现2-氨基-吩恶嗪-3-酮（吩恶嗪衍生物：Phx-3）抑制C.肺炎克雷伯氏菌在人单核细胞以及上皮细胞中的复制，部分取决于宿主细胞的聚糖代谢途径。少

Current studies have revealed that the obligate intracellular bacterium Chlamydia (Chlamydophila) pneumoniae is associated not only with respiratory diseases, but also with chronic diseases such as atherosclerosis. The detection of the C. pneumoniae DNA or antigen in coronary atherosclerotic plaque and peripheral blood of the patients with cardiovascular diseases has strengthened the likelihood of its possible involvement in the pathogenesis of atherosclerosis. Moreover, several studies indicate that viable C. pneumoniae can be detected in atherosclerotic plaques from patients of advanced age with coronary heart disease by both culture and RT-PCR methods. Our recent studies also showed that viable C. pneumoniae are readily detectable in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, indicating that the presence of viable bacteria in the blood stream might be a risk factor for the development of atherosclerosis. C. pneumoniae preferentially infects respiratory … More tract epithelial cells as well as macrophages. On the other hand, our previous studies revealed that lymphocyte is another host cell permitting C. pneumoniae infection with a persistent nature. Since lymphocytes are a major immune cell type besides macrophages in the development of atherosclerosis, interaction between lymphocytes and this pathogen may contribute to the pathogenesis of chronic inflammatory diseases associated with C. pneumoniae. We first attempted to assess a possible association between development of diabetes in non-obese diabetic (NOD) mice and dissemination of C. pneumoniae from lung to peripheral blood. By real-time reverse transcription-polymerase chain reaction (RT-PCR) with primers for C. pneumoniae 16S rRNA, following multiple intranasal inoculations,. bacteria in lung were detected in NOD mice with diabetes (38.5 %) as well as ICR mice (40 %), but prevalence of bacteria in NOD mice without diabetes (Pre-diabetic NOD mice and non-diabetic retired NOD mice) was very low (4.8 %).The bacteria were only detected in peripheral blood mononuclear cells (PBMCs) cultured withhydrocortisone of the NOD mice with diabetes (53.8 %). Results of immunostaining with fluorescein isothiocyanate-conjugated anti-chlamydia monoclonal antibody also showed the presence of bacterial antigens m the lungs and the PBMCs judged as positive by the RT-PCR. The results clearly showed that the development of diabetes in NOD mouse appears to be one of critical factors for promoting the dissemination of C. pneumoniae from lung to peripheral blood. Second, we examined a possible alteration of CD3 and CD25 expressions of human lymphocytes [Molt-4 cells and enriched lymphocytes from peripheral blood mononuclear cells (PBMCs)] by C. pneumoniae infection. The expression levels of both molecules of Molt-4 cells were significantly decreased by C. pneumoniae infection. C. pneumoniae clinical isolates also caused the alteration of both expressions of the infected cells. In contrast, C. trachomatis did not cause any alteration of both expressions of Molt-4 cells. Heat-killed bacteria and HEp-2 lysate as mock did not cause any alteration of CD3 expression of lymphocytes. Addition of either NS-398 (Cox-2 inhibitor) or AH-23848 (EP4 prostanoid receptorantagonist) tothe culture abolishedthe alteration of CD3 expression ofthe infected cells. The enhanced prostaglandin E_2 (PGE_2) productions in the culture supernatant of infected cells were also confirmed by competitiveELISA. C. pneumoniae infection of enriched lymphocytesfromPBMCs also causedanalteration of CD3 expression.Thus, C. pneumoniae infection of human lymphocytes induces an alteration of CD3 expression mediated by PGE_2 production. Since CD3 molecule has a major role in the signal transduction following antigen recognitions, such alteration may be involved in C.pneumoniae persistent infection of lymphocytes. Also, we foundthat 2-amino-phenoxazine 3-one (phenoxazine derivate: Phx-3)inhibits C. pneumoniae replication in human monocytic cells as well as epithelial cells, partially depending on the tryptophan-metabolic pathway of host cells. Less