被激活的自然杀伤细胞对结核分枝杆菌生长的控制。
Control of Mycobacterium tuberculosis growth by activated natural killer cells.
机构信息
College of Osteopathic Medicine of the Pacific Graduate of College of Biomedical Sciences Western University of Health Sciences, 309 East SecondStreet, Pomona, CA 91766, USA.
出版信息
Clin Exp Immunol. 2012 Apr;168(1):142-52. doi: 10.1111/j.1365-2249.2011.04552.x.
Abstract
We characterized the underlying mechanisms by which glutathione (GSH)-enhanced natural killer (NK) cells inhibit the growth of Mycobacterium tuberculosis (M. tb) inside human monocytes. We observed that in healthy individuals, treatment of NK cells with N-acetyl cysteine (NAC), a GSH prodrug in conjunction with cytokines such as interleukin (IL)-2 + IL-12, resulted in enhanced expression of NK cytotoxic ligands (FasL and CD40L) with concomitant stasis in the intracellular growth of M. tb. Neutralization of FasL and CD40L in IL-2 + IL-12 + NAC-treated NK cells resulted in abrogation in the growth inhibition of M. tb inside monocytes. Importantly, we observed that the levels of GSH are decreased significantly in NK cells derived from individuals with HIV infection compared to healthy subjects, and this decrease correlated with a several-fold increase in the growth of M. tb inside monocytes. This study describes a novel innate defence mechanism adopted by NK cells to control M. tb infection.
摘要
我们描述了谷胱甘肽 (GSH) 增强的自然杀伤 (NK) 细胞抑制人单核细胞内结核分枝杆菌 (M. tb) 生长的潜在机制。我们观察到，在健康个体中，用 N-乙酰半胱氨酸 (NAC) 处理 NK 细胞，NAC 是一种 GSH 前体药物，与细胞因子如白细胞介素 (IL)-2+IL-12 联合使用，导致 NK 细胞毒性配体 (FasL 和 CD40L) 的表达增强，同时 M. tb 的细胞内生长停滞。在 IL-2+IL-12+NAC 处理的 NK 细胞中中和 FasL 和 CD40L 会导致对单核细胞内 M. tb 生长抑制的丧失。重要的是，我们观察到与健康受试者相比，HIV 感染者来源的 NK 细胞中的 GSH 水平显著降低，而这种降低与 M. tb 在单核细胞内生长增加几倍相关。这项研究描述了 NK 细胞采用的一种新的先天防御机制来控制 M. tb 感染。
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