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

Shih Chang Hsu, Chien Ho Chen, Shih Han Tsai, Hirokazu Kawasaki, Chih Hsing Hung, Yu Te Chu, Hui Wen Chang, Yufeng Zhou, Jinrong Fu, Beverly Plunkett, Song Nan Su, Stefan Vieths, Reiko T. Lee, Yuan C. Lee, Shau Ku Huang

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66 Citations (Scopus)

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 (DCSIGN) 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.

Original languageEnglish
Pages (from-to)7903-7910
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number11
DOIs
Publication statusPublished - Mar 12 2010

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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    Hsu, S. C., Chen, C. H., Tsai, S. H., Kawasaki, H., Hung, C. H., Chu, Y. T., Chang, H. W., Zhou, Y., Fu, J., Plunkett, B., Su, S. N., Vieths, S., Lee, R. T., Lee, Y. C., & Huang, S. K. (2010). Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells. Journal of Biological Chemistry, 285(11), 7903-7910. https://doi.org/10.1074/jbc.M109.058370