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Neisseria meningitidis type C capsular polysaccharide inhibits lipooligosaccharide-induced cell activation by binding

Can Kocabas1, Nora Katsenelson, Sunita Kanswal

  • 1Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, 1410 Rockville Pike (HFM-428), Rockville, MD 20852-1448, USA.

Cellular Microbiology
|January 26, 2007
PubMed

Insights

The meningococcal type C capsular polysaccharide (MCPS) blocks immune responses to bacterial lipooligosaccharides (LOS). MCPS inhibits LOS-induced inflammation and immune cell maturation by binding to LOS receptors.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Neisseria meningitidis causes systemic diseases by invading mucosal barriers.
  • Activation of the innate immune system by lipooligosaccharides (LOS) is crucial for host defense.
  • Conserved meningococcal molecules are key targets for immune activation.

Purpose of the Study:

  • To investigate the role of meningococcal type C capsular polysaccharide (MCPS) in modulating host immune responses to LOS.
  • To determine the mechanism by which MCPS affects LOS-mediated immune cell activation.
  • To identify potential new virulence properties of meningococcal capsular polysaccharides.

Main Methods:

  • Monocyte and dendritic cell cultures stimulated with LOS.
  • Measurement of cytokine secretion (IL-6, TNF-alpha) and immune cell maturation markers.
  • Analysis of NF-kappaB activation and MAPK signaling pathways (ERK1/2, p38, JNK).
  • Direct binding assays of MCPS to LOS receptor components (LBP, CD14).
  • Functional assays using HEK293 cells expressing TLR4/MD-2 to assess MCPS inhibition of LOS signaling.

Main Results:

  • MCPS significantly inhibited LOS-induced IL-6 and TNF-alpha secretion from monocytes.
  • MCPS blocked LOS-induced maturation of dendritic cells.
  • MCPS suppressed LOS-induced NF-kappaB activation and MAPK signaling.
  • MCPS directly bound to LBP and CD14, inhibiting LOS binding to these receptors.
  • MCPS inhibition of LOS-mediated activation was dependent on CD14 availability.

Conclusions:

  • Meningococcal type C capsular polysaccharide (MCPS) possesses a novel virulence property by inhibiting innate immune responses to LOS.
  • MCPS interferes with the LOS-CD14-TLR4/MD-2 pathway, dampening inflammation and immune cell activation.
  • These findings reveal a mechanism by which Neisseria meningitidis may evade host immunity.

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