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

doi:10.1111/j.1462-5822.2005.00623.x

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Wiley InterScience

Cellular Microbiology

Volume 8 Issue 2, Pages 316 - 325

Published Online: 28 Sep 2005

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

Liana Steeghs ¹ *, Sandra J. van Vliet ² , Heli Uronen-Hansson ³ , Andries van Mourik ¹ , Anneke Engering ² , Martha Sanchez-Hernandez ² , Nigel Klein ³ , Robin Callard ³ , Jos P. M. van Putten ¹ , Peter van der Ley ⁴ , Yvette van Kooyk ² and Jan G. J. van de Winkel ⁵

¹ Utrecht University, Department of Infectious Diseases and Immunology, PO Box 80.165, 3508 TD Utrecht, the Netherlands.
² Vrije Universiteit Medical Center Amsterdam, Department of Molecular Cell Biology and Immunology, PO Box 7057, 1007 MB, Amsterdam, the Netherlands.
³ Institute of Child Health, University College London, Immunobiology and Infectious Disease and Microbiology Units, 30 Guilford Street, London WC1N 1EH, UK.
⁴ Netherlands Vaccine Institute, Unit Research and Development, Antonie van Leeuwenhoeklaan 11, 3721 MA Bilthoven, the Netherlands.
⁵ University Medical Center Utrecht, Department of Immunology, Immunotherapy Laboratory (KC2-085.2), Lundlaan 6, 3584EA Utrecht, the Netherlands and Genmab Utrecht, the Netherlands.

Correspondence to *E-mail l.steeghs@vet.uu.nl; Tel. (+31) 30 2534791; Fax (+31) 30 2540784.

Summary

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(β1-3)-Gal(β1-4)-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.

Received 22 February, 2005; revised 1 August, 2005; accepted 2 August, 2005.

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1462-5822.2005.00623.x About DOI