Control of Mycobacterium tuberculosis growth by activated natural killer cells

• Published in: Clinical and experimental immunology Vol. 168; no. 1; pp. 142 - 152
• Main Authors: Guerra, C., Johal, K., Morris, D., Moreno, S., Alvarado, O., Gray, D., Tanzil, M., Pearce, D., Venketaraman, V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2012; Blackwell; Oxford University Press
• Subjects: Acetylcysteine - pharmacology; Analytical, structural and metabolic biochemistry; Bacterial diseases; Biological and medical sciences; CD40 Ligand - antagonists & inhibitors; CD40 Ligand - biosynthesis; Fas Ligand Protein - biosynthesis; Female; Fundamental and applied biological sciences. Psychology; Glutathione - pharmacology; glutathione and innate immunity; HIV; HIV Infections - immunology; Human bacterial diseases; Human immunodeficiency virus; Human viral diseases; Humans; Immune system; Immunity, Innate; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Interleukin-12 - metabolism; Interleukin-2 - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - microbiology; Lymphocyte Activation; Male; Medical sciences; monocytes; Mycobacterium tuberculosis; Mycobacterium tuberculosis - growth & development; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; natural killer cells; NK Cell Lectin-Like Receptor Subfamily K - analysis; Original; Tuberculosis; Tuberculosis - immunology; Tuberculosis and atypical mycobacterial infections; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Growth; Natural immunity; Biochemistry; Mycobacterial infection; Bacteria; Glutathione; Immunopathology; monocytes; Monocyte; Retroviridae; AIDS; Immune deficiency; Lentivirus; glutathione and innate immunity; Infection; Virus; Natural killer cell; natural killer cells; Tuberculosis; Mycobacterium tuberculosis; HIV; Mycobacteriales; Viral disease; Bacteriosis; Mycobacteriaceae; Actinomycetes; Human immunodeficiency virus
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04552.x

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.