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