Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori

Nat Immunol. 2009 Oct;10(10):1081-8. doi: 10.1038/ni.1778. Epub 2009 Aug 30.


Cooperation between different innate signaling pathways induced by pattern-recognition receptors (PRRs) on dendritic cells (DCs) is crucial for tailoring adaptive immunity to pathogens. Here we show that carbohydrate-specific signaling through the C-type lectin DC-SIGN tailored cytokine production in response to distinct pathogens. DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1. Mannose-expressing Mycobacterium tuberculosis and human immunodeficiency virus type 1 (HIV-1) induced the recruitment of effector proteins to the DC-SIGN signalosome to activate Raf-1, whereas fucose-expressing pathogens such as Helicobacter pylori actively dissociated the KSR1-CNK-Raf-1 complex from the DC-SIGN signalosome. This dynamic regulation of the signalosome by mannose- and fucose-expressing pathogens led to the enhancement or suppression of proinflammatory responses, respectively. Our study reveals another level of plasticity in tailoring adaptive immunity to pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carbohydrates / immunology*
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fucose / immunology
  • HIV-1 / immunology*
  • Helicobacter pylori / immunology*
  • Humans
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Mannose / immunology
  • Microfilament Proteins / immunology
  • Microfilament Proteins / metabolism
  • Mycobacterium tuberculosis / immunology*
  • Protein Kinases / immunology
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-raf / immunology
  • Proto-Oncogene Proteins c-raf / metabolism
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*


  • Carbohydrates
  • Cell Adhesion Molecules
  • Cytokines
  • DC-specific ICAM-3 grabbing nonintegrin
  • LSP1 protein, human
  • Lectins, C-Type
  • Microfilament Proteins
  • Receptors, Cell Surface
  • Fucose
  • Protein Kinases
  • KSR-1 protein kinase
  • Proto-Oncogene Proteins c-raf
  • Mannose