Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection

Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection
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DOI:
10.1016/s0140-6736(00)03493-0
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发表时间:
2000-12-23
期刊:
影响因子:
168.9
通讯作者:
Bjune, G
Bjune, G
中科院分区:
医学1区
文献类型:
--
作者:
Hernández-Pando, R;Jeyanathan, M;Bjune, G

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背景世界上三分之一的人口具有结核分枝杆菌的潜伏感染,并且在低流行地区,大多数活动性结核病例是由于潜伏杆菌的再活化而出现的。我们试图建立这些潜伏的有机体,以促进其elimination.Methods细胞的位置,我们应用原位PCR从13个人从埃塞俄比亚和34从墨西哥谁死于肺结核以外的原因,从宏观上正常的肺组织切片。来自6名挪威人(即来自非流行性人群的人)的肺组织切片呈阴性。控制,和6个埃塞俄比亚结核病病例作为阳性controls.Findings控制尸检样本从挪威的个人都是阴性的原位PCR和传统的PCR,而所有已知的埃塞俄比亚结核病病例的样本均为阳性,这两种方法。然而,在宏观正常肺组织埃塞俄比亚和墨西哥的个人没有结核性病变,原位PCR显示5 13和10 34个阳性个体分别。这些结果通过提取DNA的常规PCR证实。阳性细胞包括肺泡和间质巨噬细胞,II型肺细胞,内皮细胞和fibroblast.Interpretation结核分枝杆菌可以持续在细胞内肺组织中没有结核性病变的组织学证据。结核分枝杆菌DNA不仅存在于巨噬细胞中,也存在于其它非专职吞噬细胞中。这些发现与传统结核病病灶中存在潜伏菌的主流观点相矛盾,并对消除潜伏和持久性杆菌的策略具有重要意义。
Background A third of the world's population has latent infection with Mycobacterium tuberculosis, and in areas of low endemicity, most cases of active tuberculosis arise as a result of reactivation of latent bacilli. We sought to establish the cellular location of these latent organisms to facilitate their elimination.Methods We applied in-situ PCR to sections of macroscopically normal lung tissue from 13 individuals from Ethiopia and 34 from Mexico who had died from causes other than tuberculosis. Sections of lung tissue from six Norwegian individuals (ie, individuals from a non-endemic population) acted as negative. controls, and six Ethiopian tuberculosis cases acted as positive controls.Findings Control necropsy samples from the Norwegian individuals were all negative by in-situ PCR and conventional PCR,whereas all samples from known Ethiopian tuberculosis cases were positive by both methods. However, in macroscopically normal lung tissue from Ethiopian and Mexican individuals without tuberculous lesions, the in-situ PCR revealed five of 13 and ten of 34 positive individuals respectively. These results were confirmed by conventional PCR with extracted DNA. Positive cells included alveolar and interstitial macrophages, type II pneumocytes, endothelial cells, and fibroblasts.Interpretation M tuberculosis can persist intracellularly in lung tissue without histological evidence of tuberculous lesions. M tuberculosis DNA is situated not only in macrophages but also inother non-professional phagocytic cells. These findings contradict the dominant view that latent organisms exist in old classic tuberculous lesions, and have important implications for strategies aimed at the elimination of latent and persistent bacilli.