title: Control of Mycobacterium tuberculosis growth by activated natural killer cells.
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.
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Guerra
authors.forename: K
authors.initials: K
authors.lastname: Johal
authors.forename: D
authors.initials: D
authors.lastname: Morris
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.forename: O
authors.initials: O
authors.lastname: Alvarado
authors.forename: D
authors.initials: D
authors.lastname: Gray
authors.forename: M
authors.initials: M
authors.lastname: Tanzil
authors.forename: D
authors.initials: D
authors.lastname: Pearce
authors.forename: V
authors.initials: V
authors.lastname: Venketaraman
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D023201:CD40 Ligand / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000032:analysis; D014376:Tuberculosis / Q000276:immunology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D023201:CD40 Ligand; D018664:Interleukin-12; D005978:Glutathione; D000111:Acetylcysteine