Gieffers J, Füllgraf H, Jahn J, Klinger M, Dalhoff K, Katus H A, Solbach W, Maass M
Institute of Medical Microbiology and Hygiene, Medical University of Lübeck, Lübeck, Germany.
Circulation. 2001 Jan 23;103(3):351-6. doi: 10.1161/01.cir.103.3.351.
Recovery of the intracellular bacterium Chlamydia pneumoniae from atherosclerotic plaques has initiated large studies on antimicrobial therapy in coronary artery disease. The basic concept that antibiotic therapy may eliminate and prevent vascular infection was evaluated in vitro and in vivo by examining the antibiotic susceptibility of C pneumoniae in circulating human monocytes, which are thought to transport chlamydiae from the respiratory tract to the vascular wall.
Blood monocytes (CD14+) from 2 healthy volunteers were obtained before and after oral treatment with azithromycin or rifampin and then inoculated with a vascular C pneumoniae strain and continuously cultured in the presence of the respective antibiotic. Progress of infection and chlamydial viability was assessed by immunogold-labeling and detection of C pneumoniae-specific mRNA transcripts. Circulating monocytes from patients undergoing treatment with experimental azithromycin for coronary artery disease were examined for C pneumoniae infection by cell culture. Antibiotics did not inhibit chlamydial growth within monocytes. Electron microscopy showed development of chlamydial inclusion bodies. Reverse transcription-polymerase chain reaction demonstrated continuous synthesis of chlamydial mRNA for 10 days without lysis of the monocytes. The in vivo presence of viable pathogen not eliminated by azithromycin was shown by cultural recovery of C pneumoniae from the circulating monocytes of 2 patients with coronary artery disease.
C pneumoniae uses monocytes as a transport system for systemic dissemination and enters a persistent state not covered by an otherwise effective antichlamydial treatment. Prevention of vascular infection by antichlamydial treatment may be problematic: circulating monocytes carrying a pathogen with reduced antimicrobial susceptibility might initiate reinfection or promote atherosclerosis by the release of proinflammatory mediators.
从动脉粥样硬化斑块中分离出细胞内细菌肺炎衣原体，引发了关于冠状动脉疾病抗菌治疗的大型研究。通过检测肺炎衣原体在循环人单核细胞中的抗生素敏感性，在体外和体内评估了抗生素治疗可能消除和预防血管感染的基本概念，这些单核细胞被认为可将衣原体从呼吸道转运至血管壁。
从2名健康志愿者身上获取血液单核细胞（CD14+），在口服阿奇霉素或利福平治疗前后进行采集，然后接种血管肺炎衣原体菌株，并在相应抗生素存在的情况下持续培养。通过免疫金标记和检测肺炎衣原体特异性mRNA转录本来评估感染进展和衣原体活力。对接受实验性阿奇霉素治疗冠状动脉疾病的患者的循环单核细胞进行细胞培养，检测是否存在肺炎衣原体感染。抗生素并未抑制单核细胞内衣原体的生长。电子显微镜显示衣原体包涵体的形成。逆转录聚合酶链反应表明，衣原体mRNA持续合成10天，单核细胞未裂解。从2名冠状动脉疾病患者的循环单核细胞中培养出肺炎衣原体，证明体内存在未被阿奇霉素清除的活病原体。
肺炎衣原体利用单核细胞作为全身播散的转运系统，并进入一种持续状态，这种状态无法被其他有效的抗衣原体治疗所覆盖。通过抗衣原体治疗预防血管感染可能存在问题：携带抗菌敏感性降低的病原体的循环单核细胞可能引发再次感染或通过释放促炎介质促进动脉粥样硬化。
