Oliveira M M, Charlab R, Pessolani M C
Laboratório de Hanseníase, Instituto Oswaldo Cruz-Fiocruz, 21045-900 Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2001 Oct;96(7):973-8. doi: 10.1590/s0074-02762001000700015.
In this study, we compared the level of TNF-alpha secretion induced in monocytic THP-1 cells after phagocytosis of Mycobacterium leprae, the causative agent of leprosy, and M. bovis BCG, an attenuated strain used as a vaccine against leprosy and tuberculosis. The presence of M. leprae and BCG was observed in more than 80% of the cells after 24 h of exposure. However, BCG but not M. leprae was able to induce TNF-alpha secretion in these cells. Moreover, THP-1 cells treated simultaneously with BCG and M. leprae secreted lower levels of TNF-alpha compared to cells incubated with BCG alone. M. leprae was able, however, to induce TNF-alpha secretion both in blood-derived monocytes as well as in THP-1 cells pretreated with phorbol myristate acetate. The inclusion of streptomycin in our cultures, together with the fact that the use of both gamma-irradiated M. leprae and heat-killed BCG gave similar results, indicate that the differences observed were not due to differences in viability but in intrinsic properties between M. leprae and BCG. These data suggest that the capacity of M. leprae to induce TNF-alpha is dependent on the stage of cell maturation and emphasize the potential of this model to explore differences in the effects triggered by vaccine strain versus pathogenic species of mycobacteria on the host cell physiology and metabolism.
在本研究中,我们比较了麻风分枝杆菌(麻风病的病原体)和卡介苗(一种用作预防麻风病和结核病的减毒菌株)被单核细胞性THP-1细胞吞噬后诱导的肿瘤坏死因子-α(TNF-α)分泌水平。暴露24小时后,在超过80%的细胞中观察到了麻风分枝杆菌和卡介苗的存在。然而,卡介苗能够在这些细胞中诱导TNF-α分泌,而麻风分枝杆菌则不能。此外,与单独用卡介苗孵育的细胞相比,同时用卡介苗和麻风分枝杆菌处理的THP-1细胞分泌的TNF-α水平更低。然而,麻风分枝杆菌能够在血液来源的单核细胞以及用佛波酯肉豆蔻酸酯预处理的THP-1细胞中诱导TNF-α分泌。我们的培养物中加入链霉素,以及使用γ射线照射的麻风分枝杆菌和热灭活的卡介苗都得到了相似结果这一事实,表明观察到的差异不是由于活力不同,而是由于麻风分枝杆菌和卡介苗之间的内在特性不同。这些数据表明,麻风分枝杆菌诱导TNF-α的能力取决于细胞成熟阶段,并强调了该模型在探索疫苗菌株与分枝杆菌致病菌种对宿主细胞生理和代谢触发的效应差异方面的潜力。