title: Carbohydrate composition of meningococcal lipopolysaccharide modulates the interaction of Neisseria meningitidis with human dendritic cells.
abstract: Meningococcal lipopolysaccharide (LPS) is of crucial importance for the pathogenesis of invasive infection. We show that sialylation and elongation of the alpha-chain effectively shields viable unencapsulated Neisseria meningitidis from recognition by human dendritic cells (DC). In contrast, beta- and gamma- chain of the LPS carbohydrate moiety play only a minor role in the interaction with DC. The protective function of the LPS for the bacteria can be counteracted in vivo by phase variation of the lgtA gene encoding LPS glycosyltransferase A. Capsule expression protects N. meningitidis efficiently from recognition and phagocytosis by DC independent of the LPS structure. Despite the significant impact of LPS composition on the adhesion and phagocytosis of N. meningitidis no differences were found in terms of cytokine levels secreted by DC for IL1-beta, IL-6, IL-8, TNF-alpha, IFN-gamma and GM-CSF. However, significantly lower levels of the regulatory mediator IL-10 were induced by encapsulated strains in comparison to isogenic unencapsulated derivatives. IL-10 secretion was shown to depend on phagocytosis because poly alpha-2,8 sialic acid did not influence IL-10 secretion. The use of truncated LPS isoforms in vaccine preparations can therefore not only result in attenuation but also in more efficient targeting of DC.
authors.affiliation: Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.forename: Corinna
authors.initials: C
authors.lastname: Schmitt
authors.forename: Heike
authors.initials: H
authors.lastname: Claus
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
authors.forename: Matthias
authors.initials: M
authors.lastname: Frosch
authors.forename: Annette
authors.initials: A
authors.lastname: Kolb-Mäurer
mesh_terms: D016667:Bacterial Capsules / Q000235:genetics / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000382:microbiology / Q000648:ultrastructure; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009345:Neisseria meningitidis / Q000235:genetics / Q000502:physiology*; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000502:physiology; D010587:Phagocytosis; D051117:Scavenger Receptors, Class A / Q000502:physiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; C505154:OpcA protein, Neisseria meningitidis; D051117:Scavenger Receptors, Class A; C090348:Opa protein, Neisseria; D016695:Glycosyltransferases; C401409:LgtA protein, bacteria; D017351:N-Acetylglucosaminyltransferases