Armstrong J A, Hart P D
J Exp Med. 1975 Jul 1;142(1):1-16. doi: 10.1084/jem.142.1.1.
Tubercle bacilli of the pathogenic human strain H37Rv had previously been shown to multiply, after ingestion by cultured mouse peritoneal macrophages, within phagosomes that tended to remain unfused with secondary lysosomes. Means were sought therefore for promoting experimentally a modification of the host response so as to attain a high level of phagolysosome formation, enabling tests to be made of any effects on the course and outcome of the intracellular infection. This was achieved by exposing viable bacilli to specific rabbit antiserum before their ingestion. Quantitative assessments, using electron microscopy, now showed that a majority of the phagosomes containing intact bacilli had fused with ferritin-labeled lysosomes, and frequently the fusion was massive. Bacterial viability studies established that the serum pretreatment was not itsel bactericidal. In the course of progressive infections with strain H37Rv, monitored by counts both of viable bacterial units and of intracellular acid-fast organisms, no appreciable difference was found between the intracellular growth rates of control and antiserum-treated bacilli. Concurrent electron microscopy showed that bacilli could remain intact and multiply both in phaagolysosomes and in unfused phagosomes, ruling out the possibility of selective growth of antiserum-pretreated bacilli within the minority of phagosomes that remained unfused. It was concluded that "turning on" phagosome-lysosome fusion in normal macrophages did not influence the outcome of infection with virulent M. tuberculosis; lysosome contents manifestly failed to exercise an antibacterial effect on this organism. Nevertheless, the possibility remains that the lysosomes of specific immune macrophages have antituberculous potentiality. In that case the experimental "turning on or off" of fusion could be a decisive factor in the outcome of a virulent challenge. Should it not be, the antibacterial capabilities of immune cells would need to be ascribed to factors other than lysosomal attack, the latter being essentially for disposal of the dead organisms.
先前已表明，致病性人类菌株H37Rv的结核杆菌在被培养的小鼠腹腔巨噬细胞摄取后，会在倾向于不与次级溶酶体融合的吞噬体内繁殖。因此，人们试图通过实验促进宿主反应的改变，以实现高水平的吞噬溶酶体形成，从而能够测试对细胞内感染过程和结果的任何影响。这是通过在活菌被摄取之前将其暴露于特异性兔抗血清中来实现的。现在，利用电子显微镜进行的定量评估表明，大多数含有完整杆菌的吞噬体已与铁蛋白标记的溶酶体融合，而且融合常常是大量的。细菌活力研究证实，血清预处理本身并无杀菌作用。在用H37Rv菌株进行的进行性感染过程中，通过对活菌单位和细胞内抗酸菌的计数进行监测，发现对照杆菌和经抗血清处理的杆菌在细胞内的生长速率没有明显差异。同时进行的电子显微镜检查表明，杆菌既能在吞噬溶酶体内也能在未融合的吞噬体内保持完整并繁殖，排除了抗血清预处理的杆菌在少数未融合的吞噬体内选择性生长的可能性。得出的结论是，在正常巨噬细胞中“开启”吞噬体-溶酶体融合并不影响毒力结核分枝杆菌感染的结果；溶酶体内容物显然未能对该生物体发挥抗菌作用。然而，特异性免疫巨噬细胞的溶酶体仍有可能具有抗结核潜力。在这种情况下，实验性地“开启或关闭”融合可能是毒力攻击结果的决定性因素。如果不是这样，免疫细胞的抗菌能力就需要归因于溶酶体攻击以外的因素，后者基本上是用于处理死亡生物体的。
