Induction of Th1/Th17 immune response by Mycobacterium tuberculosis: role of dectin-1, Mannose Receptor, and DC-SIGN

J Leukoc Biol. 2009 Dec;86(6):1393-401. doi: 10.1189/jlb.0409242. Epub 2009 Sep 22.

Abstract

Mtb influences DC activity and T cell-mediated immune responses. We show that the treatment of immature monocyte-derived DC with Mtb elicited the formation of mature DC, producing TNF-alpha, IL-1beta, IL-6, and IL-23 and instructing CD4(+) cells to secrete IFN-gamma and IL-17. Mtb-induced cytokine release by DC depended on dectin-1 receptor engagement, whereas MR or DC-SIGN stimulation inhibited this process. A selective dectin-1 binding by the receptor agonist glucan was sufficient to enable DC to generate Th1/Th17 lymphocytes, showing features comparable with those induced by Mtb-treated DC. Interestingly, DC-SIGN or MR engagement inhibited Th17 and increased Th1 generation by glucan- or Mtb-treated DC. Our results indicate that Mtb modulates the lymphocyte response by affecting DC maturation and cytokine release. Dectin-1 engagement by Mtb enables DC to promote a Th1/Th17 response, whereas DC-SIGN and MR costimulation limits dectin-1-dependent Th17 generation and favors a Th1 response, probably by interfering with release of cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / immunology*
  • Cells, Cultured
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Humans
  • Lectins, C-Type / immunology*
  • Mannose Receptor
  • Mannose-Binding Lectins / immunology*
  • Membrane Proteins / immunology*
  • Monocytes / immunology*
  • Mycobacterium tuberculosis / immunology*
  • Nerve Tissue Proteins / immunology*
  • Receptors, Cell Surface / immunology*
  • Th1 Cells / immunology*

Substances

  • Cell Adhesion Molecules
  • Cytokines
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • dectin 1