Functional Interaction of Common Allergens and a C-type Lectin Receptor, Dendritic Cell-specific ICAM3-grabbing Non-integrin (DC-SIGN), on Human Dendritic Cells

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 function...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2010-03, Vol.285 (11), p.7903-7910
Main Authors: Hsu, Shih-Chang, Chen, Chien-Ho, Tsai, Shih-Han, Kawasaki, Hirokazu, Hung, Chih-Hsing, Chu, Yu-Te, Chang, Hui-Wen, Zhou, Yufeng, Fu, Jinrong, Plunkett, Beverly, Su, Song-Nan, Vieths, Stefan, Lee, Reiko T., Lee, Yuan C., Huang, Shau-Ku
Format: Article
Language:English
Subjects:
Allergens - immunology
Allergens - metabolism
Allergens - pharmacology
Animals
Antigen
C-type Lectin
Carbohydrate/Glycoprotein
Cell Adhesion Molecules - immunology
Cell Adhesion Molecules - metabolism
Cynodon - immunology
Cytokines
Dendritic Cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dermatophagoides pteronyssinus
Glycobiology and Extracellular Matrices
Humans
Immunology/Antigen
Immunology/Innate Immunity
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 α1,3-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 (Lex). 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-α 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-α expression in MDDCs via, in part, Raf-1 signaling pathways.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.058370