Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function

Liana Steeghs, Sandra J van Vliet, Heli Uronen-Hansson, Andries van Mourik, Anneke Engering, Martha Sanchez-Hernandez, Nigel Klein, Robin Callard, Jos P M van Putten, Peter van der Ley, Yvette van Kooyk, Jan G J van de Winkel

Research output: Contribution to journalArticleAcademicpeer-review

75 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)316-25
Number of pages10
JournalCellular microbiology
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2006

Keywords

  • Antigen Presentation
  • Bacterial Adhesion
  • Cell Adhesion Molecules/metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines/biosynthesis
  • Dendritic Cells/immunology
  • Humans
  • Lectins, C-Type/metabolism
  • Lipopolysaccharides/metabolism
  • Mutation
  • Neisseria meningitidis/genetics
  • Oligosaccharides/genetics
  • Receptors, Cell Surface/metabolism
  • Th1 Cells/cytology
  • Th2 Cells/cytology

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