Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells

J Biol Chem. 2010 Mar 12;285(11):7903-10. doi: 10.1074/jbc.M109.058370. Epub 2010 Jan 15.

Abstract

Fucosylated glycans on pathogens are known to shape the immune response through their interaction with pattern recognition receptors, such as C-type lectin receptors (CLRs), on dendritic cells (DCs). Similar fucosylated structures are also commonly found in a variety of allergens, but their functional significance remains unclear. To test a hypothesis that allergen-associated glycans serve as the molecular patterns in functional interaction with CLRs, an enzyme-linked immunosorbent assay-based binding assay was performed to determine the binding activity of purified allergens and allergen extracts. THP-1 cells and monocyte-derived DCs (MDDCs) were investigated as a model for testing the functional effects of allergen-CLR interaction using enzyme-linked immunosorbent assay, Western blotting, and flow cytometry. Significant and saturable bindings of allergens and allergen extracts with variable binding activities to DC-specific ICAM3-grabbing non-integrin (DC-SIGN) and its related receptor, L-SIGN, were found. These include bovine serum albumin coupled with a common glycoform (fucosylated glycan lacking the alpha1,3-linked mannose) of allergens and a panel of purified allergens, including BG60 (Cyn dBG-60; Bermuda grass pollen) and Der p2 (house dust mite). The binding activity was calcium-dependent and inhibitable by fucose and Lewis-x trisaccharides (Le(x)). In THP-1 cells and human MDDCs, BG60-DC-SIGN interaction led to the activation of Raf-1 and ERK kinases and the induction of tumor necrosis factor-alpha expression. This effect could be blocked, in part, by Raf-1 inhibitor or anti-DC-SIGN antibodies and was significantly reduced in cells with DC-SIGN knockdown. These results suggest that allergens are able to interact with DC-SIGN and induce tumor necrosis factor-alpha expression in MDDCs via, in part, Raf-1 signaling pathways.

Publication types

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

MeSH terms

  • Allergens / immunology*
  • Allergens / metabolism
  • Allergens / pharmacology
  • Animals
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cynodon / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Monocytes / cytology
  • Pollen / immunology
  • Polysaccharides / immunology
  • Polysaccharides / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Pyroglyphidae / immunology
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Serum Albumin, Bovine / immunology
  • Serum Albumin, Bovine / pharmacology
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Allergens
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Polysaccharides
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • Serum Albumin, Bovine
  • Proto-Oncogene Proteins c-raf