title: Mannose binding lectin enhances IL-1beta and IL-10 induction by non-lipopolysaccharide (LPS) components of Neisseria meningitidis.
abstract: Mannose binding lectin (MBL) is a key molecule in the lectin pathway of complement activation, and likely of importance in our innate defence against meningococcal infection. We evaluated the role of MBL in cytokine induction by LPS or non-LPS components of Neisseria meningitidis, using a meningococcal mutant deficient for LPS. Binding experiments showed that MBL exhibited low, but significant binding to encapsulated LPS+ meningococci (H44/76) and LPS-deficient (LPS-) meningococci (H44/76lpxA). Experiments with human mononuclear cells (PBMCs) showed that MBL significantly augmented IL-1beta production after stimulation with LPS+ and LPS- meningococci, in a dose-dependent fashion. In addition, IL-10 production was enhanced after stimulation with LPS- meningococci. In contrast, TNFalpha, IL-6 and IFNgamma productions were unaffected. No effect of MBL was observed on cytokine induction by meningococcal LPS. MBL enhanced cytokine production at concentrations >10(7) meningococci. It is concluded that MBL interacts with non-LPS components of N. meningitidis and in this way modulates the cytokine response.
authors.affiliation: Department of General Internal Medicine, University Medical Centre St Radboud, Nijmegen, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Dominic L
authors.initials: DL
authors.lastname: Jack
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Klein
authors.forename: Malcolm W
authors.initials: MW
authors.lastname: Turner
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Liana
authors.initials: L
authors.lastname: Steeghs
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Jacobs
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin / Q000097:blood / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma