Interleukin-17A differentially modulates BCG induction of cytokine production in human blood macrophages

J Leukoc Biol. 2011 Aug;90(2):333-41. doi: 10.1189/jlb.0510311. Epub 2011 Apr 26.


The pathogenesis of Mtb depends in part on cytokine cross-regulation between macrophages and T cells in host immunity. Th17 cells produce IL-17A to induce granuloma formation and to restrict mycobacterial dissemination. IL-17A also mediates cytokine responses induced by proinflammatory cytokines such as TNF-α. Our previous results showed that BCG induces IL-6, IL-10, and TNF-α via activity of protein kinases, including dsRNA-activated serine/threonine protein kinase and glycogen synthase kinase-3 in primary human monocytes. Therefore, we investigated whether IL-17A, upon its induction by BCG, plays an additional role to aid the production of downstream proinflammatory cytokines in macrophages. Here, we showed that IL-17A enhanced IL-6 mRNA and protein levels inducible by BCG in a time- and dose-dependent manner, whereas it had no effect on IL-10 and TNF-α production. We also demonstrated that IL-17A activated the phosphorylation of ERK1/2 triggered by BCG. With the use of a specific chemical inhibitor of a MAPK/ERK-activating kinase (MEK1/2), we confirmed the correlation between the enhanced ERK1/2 activation and augmented IL-6 production. Additionally, we revealed that IL-17A acts in concert with BCG-induced TNF-α to enhance the level of IL-6 synthesis. Taken together, our results suggest a significant role of IL-17A to serve as a modulator of cytokine expression in innate immune response during mycobacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / biosynthesis*
  • Humans
  • Immunity, Innate
  • Interleukin-17 / immunology*
  • Macrophages / metabolism*
  • Macrophages / virology
  • Mycobacterium Infections / immunology
  • Mycobacterium bovis / immunology*
  • Transcriptional Activation / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • Interleukin-17
  • Tumor Necrosis Factor-alpha