Control of Mycobacterium tuberculosis growth by activated natural killer cells

被引:60
作者
Guerra, C.
Johal, K.
Morris, D. [2 ]
Moreno, S. [2 ]
Alvarado, O.
Gray, D.
Tanzil, M.
Pearce, D.
Venketaraman, V. [1 ]
机构
[1] Western Univ Hlth Sci, Dept Basic Med Sci, Coll Osteopath Med Pacific, Pomona, CA 91766 USA
[2] Grad Coll Biomed Sci, Pomona, CA USA
关键词
glutathione and innate immunity; HIV; monocytes; natural killer cells; tuberculosis; SURFACE-MOLECULE; GLUTATHIONE; CYTOTOXICITY; LIGAND; NITROSOGLUTATHIONE; INDUCTION; HIV;
D O I
10.1111/j.1365-2249.2011.04552.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:142 / 152
页数:11
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