Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor

J Immunol. 2001 Jun 15;166(12):7477-85. doi: 10.4049/jimmunol.166.12.7477.

Abstract

IL-12 is a key cytokine in directing the development of type 1 Th cells, which are critical to eradicate intracellular pathogens such as Mycobacterium tuberculosis. Here, we report that mannose-capped lipoarabinomannans (ManLAMs) from Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis inhibited, in a dose-dependent manner, the LPS-induced IL-12 production by human dendritic cells. The inhibitory activity was abolished by the loss of the mannose caps or the GPI acyl residues. Mannan, which is a ligand for the mannose receptor (MR) as well as an mAb specific for the MR, also inhibited the LPS-induced IL-12 production by dendritic cells. Our results indicate that ManLAMs may act as virulence factors that contribute to the persistence of M. bovis bacillus Calmette-Guérin and M. tuberculosis within phagocytic cells by suppressing IL-12 responses. Our data also suggest that engagement of the MR by ManLAMs delivers a negative signal that interferes with the LPS-induced positive signals delivered by the Toll-like receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Cells, Cultured
  • Chemical Fractionation
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dose-Response Relationship, Immunologic
  • Glycosylphosphatidylinositols / chemistry
  • Glycosylphosphatidylinositols / immunology
  • Humans
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / metabolism
  • Lectins, C-Type*
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / immunology*
  • Lipopolysaccharides / isolation & purification
  • Lipopolysaccharides / metabolism*
  • Mannans / metabolism
  • Mannose / metabolism*
  • Mannose-Binding Lectins*
  • Molecular Sequence Data
  • Mycobacterium bovis / immunology
  • Mycobacterium tuberculosis / immunology
  • Receptors, Cell Surface / physiology*
  • Signal Transduction / immunology*

Substances

  • Glycosylphosphatidylinositols
  • Lectins, C-Type
  • Lipopolysaccharides
  • Mannans
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • lipoarabinomannan
  • mannose receptor
  • Interleukin-12
  • Mannose