Control of  Mycobacterium tuberculosis  growth by activated natural killer cells | Zendy

Guerra C. | Zendy; Johal K. | Zendy; Morris D. | Zendy; Moreno S. | Zendy; Alvarado O. | Zendy; Gray D. | Zendy; Tanzil M. | Zendy; Pearce D. | Zendy; Venketaraman V. | Zendy

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Control of Mycobacterium tuberculosis growth by activated natural killer cells

Author(s) -

Guerra C.,

Johal K.,

Morris D.,

Moreno S.,

Alvarado O.,

Gray D.,

Tanzil M.,

Pearce D.,

Venketaraman V.

Publication year - 2012

Publication title -

clinical & experimental immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.329

H-Index - 135

eISSN - 1365-2249

pISSN - 0009-9104

DOI - 10.1111/j.1365-2249.2011.04552.x

Subject(s) - immunology , cytotoxic t cell , mycobacterium tuberculosis , biology , interleukin 12 , interferon gamma , interleukin 21 , glutathione , natural killer cell , immune system , cd8 , tuberculosis , medicine , biochemistry , pathology , in vitro , enzyme

Summary 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.

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