Bermudez L E, Young L S
Kuzell Institute for Arthritis and Infectious Diseases, Pacific Presbyterian Medical Center, San Francisco, CA 94115.
J Immunol. 1991 Jan 1;146(1):265-70.
Host defense mechanisms against Mycobacterium avium complex (MAC) are poorly understood. Recent evidence suggests the role of NK cells in the host defense against some intracellular pathogens. We investigated whether NK cells play a role in MAC infection. IL-2-activated human NK cells were incubated with human monocyte-derived macrophages either before or after infection with MAC. Macrophages were lysed 3 and 5 days after infection for quantitation of viable intracellular organisms. Although no killing was observed by nonstimulated macrophages, exposure to IL-2-treated NK cells for 24 h before infection induced macrophage to kill 70 +/- 8% of intracellular MAC by 3 days, and 81% +/- 4% in 5 days (p less than 0.01 for both compared with control). Killing was not blocked by incubation with anti-TNF antibody (Ab) or anti-IFN-gamma Ab. Similarly, incubation of macrophages for 24 h with supernatant obtained from IL-2 activated NK cells was associated with 74 +/- 4% killing of intracellular MAC in 3 days and 81 +/- 6% in 5 days (p less than 0.01 for both compared with control). However, the supernatant-mediated activation was partially blocked by anti-TNF Ab (46 +/- 6%; p less than 0.05) but not by anti-IFN gamma Ab. When infected macrophages were incubated with NK cells 24 h after infection for 48 h, they killed 54 +/- 3% of intracellular M. avium in 3 days and 73 +/- 5% in 5 days (p less than 0.02 for both compared with control). This effect was also not blocked by either anti-TNF or anti-IFN gamma Ab. These results suggest that activated NK cells may have an important role in the intracellular killing of MAC and that the NK-mediated activation of macrophages is in part mediated by TNF.
人们对宿主针对鸟分枝杆菌复合群（MAC）的防御机制了解甚少。最近有证据表明自然杀伤（NK）细胞在宿主抵御某些细胞内病原体的防御中发挥作用。我们研究了NK细胞在MAC感染中是否发挥作用。将白细胞介素-2（IL-2）激活的人NK细胞在感染MAC之前或之后与人单核细胞衍生的巨噬细胞一起孵育。感染后3天和5天裂解巨噬细胞，以定量存活的细胞内微生物。虽然未刺激的巨噬细胞未观察到杀伤作用，但在感染前将其暴露于经IL-2处理的NK细胞24小时，可诱导巨噬细胞在3天时杀死70±8%的细胞内MAC，5天时杀死81%±4%（与对照组相比，两者p均小于0.01）。与抗肿瘤坏死因子（TNF）抗体或抗干扰素-γ抗体孵育不会阻断杀伤作用。同样，将巨噬细胞与从IL-2激活的NK细胞获得的上清液孵育24小时，在3天时可杀死74±4%的细胞内MAC，5天时杀死81±6%（与对照组相比，两者p均小于0.01）。然而，上清液介导的激活被抗TNF抗体部分阻断（46±6%；p小于0.05），但未被抗干扰素-γ抗体阻断。当感染的巨噬细胞在感染后24小时与NK细胞孵育48小时，它们在3天时杀死54±3%的细胞内鸟分枝杆菌，5天时杀死73±5%（与对照组相比，两者p均小于0.02）。这种作用也未被抗TNF或抗干扰素-γ抗体阻断。这些结果表明，激活的NK细胞可能在细胞内杀伤MAC中起重要作用，并且NK介导的巨噬细胞激活部分由TNF介导。
