Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function |
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Authors: | Steeghs Liana van Vliet Sandra J Uronen-Hansson Heli van Mourik Andries Engering Anneke Sanchez-Hernandez Martha Klein Nigel Callard Robin van Putten Jos P M van der Ley Peter van Kooyk Yvette van de Winkel Jan G J |
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Institution: | Utrecht University, Department of Infectious Diseases and Immunology, PO Box 80.165, 3508 TD Utrecht, the Netherlands. l.steeghs@vet.uu.nl |
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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. |
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