Proinflammatory responses to lipo-oligosaccharide of Neisseria meningitidis immunotype strains in relation to virulence and disease.
Inflammatory responses to lipo-oligosaccharide (LOS) contribute to the severity of meningococcal disease. Strains that express the L(3,7,9) LOS immunotypes are isolated from the majority of patients, but other immunotypes are isolated predominantly from carriers. Inflammatory responses elicited from a human monocytic cell line (THP-1) that had been pretreated with vitamin D3 (VD3) were compared after stimulation with purified LOSs from standard immunotype strains. The neutralizing effects of normal human serum and serum from mice immunized with strain B:2a:P1.5,2:L3 were compared. LOSs of immunotypes L3, L7, L8, and L9 induced significantly higher levels of tumor necrosis factor-alpha and interleukin-6, compared with other immunotypes. Normal human serum neutralized the proinflammatory responses to LOSs of all immunotypes tested. Immune mouse serum neutralized inflammatory responses against LOSs from immunotypes with epitopes cross-reactive with L(3,7,9) moieties. Antibodies found in normal human serum and immune mouse serum to the oligosaccharide, core, and lipid A moieties of meningococcal endotoxin contribute to neutralizing activity.
Braun
Jan M
JM
Medical Microbiology, University of Edinburgh Medical School, Edinburgh, Scotland and Institute for Scientific Evaluation of Naturopathy, University of Cologne Medical School, Cologne, Germany. matthias.braun@medizin.uni-koeln.de
Blackwell
Caroline C
CC
Poxton
Ian R
IR
El Ahmer
Omar
O
Gordon
Ann E
AE
Madani
Osama M Al
OM
Weir
Donald M
DM
Giersen
Sonja
S
Beuth
Josef
J
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D002460:Cell Line; D002762:Cholecalciferol; D004731:Endotoxins / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis*; D008050:Lipid A / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D008589:Meningococcal Infections / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D009500:Neutralization Tests; D009844:Oligosaccharides / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014774:Virulence
D000907:Antibodies, Bacterial; D004731:Endotoxins; D000939:Epitopes; D007106:Immune Sera; D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D014409:Tumor Necrosis Factor-alpha; C042058:core endotoxin; C023023:lipid-linked oligosaccharides; D002762:Cholecalciferol