Contributions of Neisseria Meningitidis LPS and non-LPS to Proinflammatory Cytokine Response

J Leukoc Biol. 2001 Aug;70(2):283-8.

Abstract

To determine the relative contribution of lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis to the pathogenesis of meningococcal sepsis, this study quantitatively compared cytokine induction by isolated LPS, wild-type serogroup B meningococci (strain H44/76), and LPS-deficient mutant meningococci (strain H44/76[pLAK33]). Stimulation of human peripheral-blood mononuclear cells with wild-type and LPS-deficient meningococci showed that non-LPS components of meningococci are responsible for a substantial part of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production and virtually all interferon (IFN)-gamma production. Based on tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LPS in proteinase K-treated lysates of N. meningitidis H44/76, a quantitative comparison was made between the cytokine-inducing capacity of isolated and purified LPS and LPS-containing meningococci. At concentrations of >10(7) bacteria/mL, intact bacteria were more potent cytokine inductors than equivalent amounts of isolated LPS, and cytokine induction by non-LPS components was additive to that by LPS. Experiments with mice showed that non-LPS components of meningococci were able to induce cytokine production and mortality. The principal conclusion is that non-LPS parts of N. meningitidis may play a role in the pathogenesis of meningococcal sepsis by inducing substantial TNF-alpha, IL-1beta, and IFN-gamma production.

MeSH terms

  • Animals
  • Bacterial Outer Membrane Proteins / pharmacology
  • Cytokines / biosynthesis*
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation Mediators / metabolism
  • Interferon-gamma / biosynthesis
  • Interleukin-1 / biosynthesis
  • Leukocytes, Mononuclear / drug effects
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects
  • Meningococcal Infections / etiology
  • Mice
  • Mice, Inbred C57BL
  • Neisseria meningitidis / chemistry*
  • Sepsis / etiology
  • Sepsis / mortality
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Bacterial Outer Membrane Proteins
  • Cytokines
  • Inflammation Mediators
  • Interleukin-1
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma