Control of Mycobacterium tuberculosis growth by activated natural killer cells
Control of Mycobacterium tuberculosis growth by activated natural killer cells
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DOI：
10.1111/j.1365-2249.2011.04552.x
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发表时间：
2012-04-01
影响因子：
4.6
通讯作者：
Venketaraman, V.
中科院分区：
文献类型：
--
作者：
Guerra, C.;Johal, K.;Venketaraman, V.
我们描述了谷胱甘肽（GSH）增强的自然杀伤（NK）细胞抑制结核分枝杆菌生长的潜在机制。结核病）在人类单核细胞内。我们观察到，在健康个体中，用N-乙酰半胱氨酸（NAC）（一种GSH前药）与细胞因子（如白细胞介素（IL）-2 + IL-12）联合治疗NK细胞，导致NK细胞毒性配体（FasL和CD 40 L）表达增强，同时M细胞内生长停滞。TB. IL-2 + IL-12 + NAC处理的NK细胞中FasL和CD 40 L的中和导致M.单核细胞内的结核病。重要的是，我们观察到，与健康受试者相比，来自HIV感染者的NK细胞中的GSH水平显着降低，并且这种降低与M的生长增加几倍相关。单核细胞内的结核病。这项研究描述了一种新的天然防御机制，通过NK细胞控制M。肺结核感染。
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.