title: Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.
abstract: Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.
authors.affiliation: Utrecht University, Department of Infectious Diseases and Immunology, PO Box 80.165, 3508 TD Utrecht, the Netherlands. l.steeghs@vet.uu.nl
authors.forename: Liana
authors.initials: L
authors.lastname: Steeghs
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.forename: Heli
authors.initials: H
authors.lastname: Uronen-Hansson
authors.forename: Andries
authors.initials: A
authors.lastname: van Mourik
authors.forename: Anneke
authors.initials: A
authors.lastname: Engering
authors.forename: Martha
authors.initials: M
authors.lastname: Sanchez-Hernandez
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.forename: Robin
authors.initials: R
authors.lastname: Callard
authors.forename: Jos P M
authors.initials: JP
authors.lastname: van Putten
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Jan G J
authors.initials: JG
authors.lastname: van de Winkel
mesh_terms: D017951:Antigen Presentation; D001422:Bacterial Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C013084:lacto-N-neotetraose