Falcone V, Bassey E B, Toniolo A, Conaldi P G, Collins F M
Institute of Medicine and Public Health, University of Pavia, Varese, Italy.
FEMS Immunol Med Microbiol. 1994 Mar;8(3):225-32. doi: 10.1111/j.1574-695X.1994.tb00447.x.
The ability of Mycobacterium tuberculosis H37Rv and H37Ra, M. bovis BCG and M. smegmatis to induce the secretion of tumor necrosis factor-alpha (TNF-alpha) by cultured murine peritoneal macrophages is inversely related to their virulence. The avirulent species of mycobacteria which were unable to persist in macrophages were capable of inducing significant levels of TNF-alpha compared to that formed in cultures infected with the virulent M. tuberculosis H37Rv. This difference was also associated with an inherent toxicity by live H37Rv for macrophage cultures. Heat-killed H37Rv was non-toxic and induced significant levels of TNF-alpha; in contrast, live and heat-killed suspensions of avirulent mycobacteria had an equivalent ability to trigger TNF-alpha secretion. The TNF-alpha response was dose-dependent, related directly to the percentage of infected cells, and peaked 6-12 h post-infection. An early and vigorous TNF-alpha response appears to be a marker of macrophage resistance, while the downregulation of this response seems associated with macrophage toxicity and unrestricted mycobacterial growth.
结核分枝杆菌H37Rv和H37Ra、牛分枝杆菌卡介苗（M. bovis BCG）以及耻垢分枝杆菌（M. smegmatis）诱导培养的小鼠腹腔巨噬细胞分泌肿瘤坏死因子-α（TNF-α）的能力与其毒力呈负相关。与感染有毒力的结核分枝杆菌H37Rv的培养物相比，无法在巨噬细胞中持续存在的无毒力分枝杆菌能够诱导产生显著水平的TNF-α。这种差异还与活的H37Rv对巨噬细胞培养物的固有毒性有关。热灭活的H37Rv无毒且能诱导产生显著水平的TNF-α；相反，无毒力分枝杆菌的活菌悬液和热灭活悬液触发TNF-α分泌的能力相当。TNF-α反应呈剂量依赖性，直接与感染细胞的百分比相关，在感染后6 - 12小时达到峰值。早期且强烈的TNF-α反应似乎是巨噬细胞抗性的一个标志，而这种反应的下调似乎与巨噬细胞毒性和分枝杆菌不受限制的生长有关。
