title: Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells.
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.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Hsu
authors.forename: Chien-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Shih-Han
authors.initials: SH
authors.lastname: Tsai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Chu
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jinrong
authors.initials: J
authors.lastname: Fu
authors.forename: Beverly
authors.initials: B
authors.lastname: Plunkett
authors.forename: Song-Nan
authors.initials: SN
authors.lastname: Su
authors.forename: Stefan
authors.initials: S
authors.lastname: Vieths
authors.forename: Reiko T
authors.initials: RT
authors.lastname: Lee
authors.forename: Yuan C
authors.initials: YC
authors.lastname: Lee
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D031744:Cynodon / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D011058:Pollen / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000485:Allergens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011134:Polysaccharides; D019908:Proto-Oncogene Proteins c-raf; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin