Mannose binding lectin enhances IL-1beta and IL-10 induction by non-lipopolysaccharide (LPS) components of Neisseria meningitidis.
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.
Sprong
Tom
T
Department of General Internal Medicine, University Medical Centre St Radboud, Nijmegen, The Netherlands.
Jack
Dominic L
DL
Klein
Nigel J
NJ
Turner
Malcolm W
MW
van der Ley
Peter
P
Steeghs
Liana
L
Jacobs
Liesbeth
L
van der Meer
Jos W M
JW
van Deuren
Marcel
M
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
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma