Filley E A, Rook G A
Department of Medical Microbiology, School of Pathology, University College and Middlesex School of Medicine, London, United Kingdom.
Infect Immun. 1991 Aug;59(8):2567-72. doi: 10.1128/iai.59.8.2567-2572.1991.
Unlike Mycobacterium leprae, Mycobacterium tuberculosis is not found inside cells other than macrophages and polymorphonuclear cells in vivo, yet previous work has revealed that in vitro it readily enters all cell lines tested. Moreover, these cells are not killed by the intracellular mycobacteria. We report here that when fibroblasts take up live (but not killed) M. tuberculosis H37Rv, they develop greatly increased sensitivity to the toxic effects of tumor necrosis factor (TNF) whether the cell line is inherently sensitive to TNF or not. Ultrasonically disrupted M. tuberculosis also has this property. The increased sensitivity is seen in the absence of metabolic inhibitors, although addition of emetine, an inhibitor of protein synthesis, causes the effect to manifest itself earlier and at a lower concentration of TNF. In contrast, infection with Mycobacterium bovis bacillus Calmette-Guérin induces little or no increased sensitivity to TNF, whereas Mycobacterium avium and M. tuberculosis H37Ra have intermediate sensitivities. We discuss the possibility that virulent tuberculosis strains produce a factor which distorts the normal protective function of TNF, rendering it toxic to host tissues and leading to the classical immunopathology of tuberculous lesions.
与麻风分枝杆菌不同，结核分枝杆菌在体内除巨噬细胞和多形核细胞外不会在其他细胞内发现，但先前的研究表明，在体外它很容易进入所有测试的细胞系。此外，这些细胞不会被细胞内的分枝杆菌杀死。我们在此报告，当成纤维细胞摄取活的（而非杀死的）结核分枝杆菌H37Rv时，无论该细胞系对肿瘤坏死因子（TNF）是否具有固有敏感性，它们对TNF的毒性作用的敏感性都会大大增加。超声破碎的结核分枝杆菌也具有这种特性。即使在没有代谢抑制剂的情况下也能观察到敏感性增加，尽管添加蛋白质合成抑制剂吐根碱会使这种效应在较低浓度的TNF下更早显现。相比之下，用卡介苗感染牛分枝杆菌对TNF的敏感性几乎没有增加或没有增加，而鸟分枝杆菌和结核分枝杆菌H37Ra具有中等敏感性。我们讨论了毒力强的结核菌株产生一种因子的可能性，该因子会扭曲TNF的正常保护功能，使其对宿主组织产生毒性，并导致结核病变的经典免疫病理学。
