title: Particulate β-glucans synergistically activate TLR4 and Dectin-1 in human dendritic cells.
abstract: The major receptor for β(1-3)-glucans on immune cells is considered to be Dectin-1 receptor. Particulate β-glucans induce stronger immune responses than soluble β-glucans by clustering of Dectin-1 receptors. Here, it was hypothesized that activation of other pattern recognition receptors such as Toll-like receptor 4 (TLR4) can also contribute to enhanced activity of immune cells after exposure to particulate β-glucans.
  
  
  
  To test this hypothesis, reporter cell lines were designed expressing TLR4 with either Dectin-1A or Dectin-1B, that is, one of the two transcript variants of human Dectin-1 receptors. Enhanced NF-κB activation was observed after stimulation with particulate β-glucans in both Dectin-1A-TLR4 and the Dectin-1B-TLR4 cell lines. This was different with soluble β-glucans, which enhanced activation in Dectin-1A-TLR4 cell lines but not in Dectin-1B-TLR4 cells. The synergistic activation of TLR4 and Dectin-1 by particulate β-glucans was confirmed in human dendritic cells. The effects of particulate β-glucan induced TLR4 binding were regulatory as blocking TLR4 enhanced pro-inflammatory cytokine IL-23, IL-4, IL-6, and TNF-α production.
  
  
  
  These results suggest that TLR4 and Dectin-1 are synergistically activated by particulate β-glucans, wherein TLR4 activates an immune regulatory pathway in human dendritic cells. Our data suggest that β-glucan is an immune regulatory ligand for TLR4.
authors.affiliation: Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Neha M
authors.initials: NM
authors.lastname: Sahasrabudhe
authors.affiliation: Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jelleke
authors.initials: J
authors.lastname: Dokter-Fokkens
authors.affiliation: Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D015847:Interleukin-4; D015850:Interleukin-6; D037181:Lectins, C-Type; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D000099181:Dectin-1; C546929:CLEC7A protein, human
keywords: Dectin-1; Dietary fiber; Immunomodulation; TLR4; β-Glucan