Differential modulation of TNF-alpha-induced apoptosis by Neisseria meningitidis

Ala-Eddine Deghmane1, Carole Veckerlé, Dario Giorgini

  • 1Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France. ala-eddine.deghmane@pasteur.fr

Plos Pathogens
|May 5, 2009
PubMed

Insights

Neisseria meningitidis causes asymptomatic carriage or severe disease. Pathogenic strains induce apoptosis and inflammation via lipooligosaccharide, while carriage strains protect nasopharyngeal cells from damage.

Area of Science:

  • Microbiology
  • Immunology
  • Cell Biology

Background:

  • Neisseria meningitidis exhibits a dichotomy between asymptomatic carriage and severe invasive disease.
  • The bacterial and host factors governing this balance remain incompletely understood.
  • Cytopathic effects and cellular damage are implicated in the pathogenesis of hyper-invasive meningococcal lineages.

Purpose of the Study:

  • To investigate the distinct cell-bacteria interactions between pathogenic and carriage Neisseria meningitidis isolates.
  • To elucidate the mechanisms underlying differential host cell responses to meningococcal infection.

Main Methods:

  • Infection of human epithelial cells with pathogenic (ST-11 complex) and carriage meningococcal isolates.
  • Assessment of cytopathic effects and apoptosis using FITC-Annexin V staining, FACS analysis, caspase assays, and DNA fragmentation.
  • Quantification of bioactive Tumor Necrosis Factor-alpha (TNF-alpha) and shedding of TNF-alpha Receptor I (TNF-RI).

Main Results:

  • Pathogenic meningococcal isolates induced significant apoptosis in human epithelial cells, primarily mediated by lipooligosaccharide (endotoxin).
  • Bioactive TNF-alpha was detected exclusively during infection with pathogenic isolates.
  • Carriage isolates induced shedding of TNF-RI, conferring protection against TNF-alpha-mediated apoptosis.

Conclusions:

  • The capacity to induce apoptosis and inflammation are critical virulence factors in Neisseria meningitidis pathogenesis.
  • Carriage isolates of Neisseria meningitidis actively modulate host responses by reducing inflammation and apoptosis.
  • This modulation likely facilitates the persistence of carriage strains within the nasopharyngeal niche, protecting their ecological habitat.

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