Skip to main content
Article thumbnail
Location of Repository

Differential Modulation of TNF-α–Induced Apoptosis by Neisseria meningitidis

By Ala-Eddine Deghmane, Carole Veckerlé, Dario Giorgini, Eva Hong, Corinne Ruckly and Muhamed-Kheir Taha


Infections by Neisseria meningitidis show duality between frequent asymptomatic carriage and occasional life-threatening disease. Bacterial and host factors involved in this balance are not fully understood. Cytopathic effects and cell damage may prelude to pathogenesis of isolates belonging to hyper-invasive lineages. We aimed to analyze cell–bacteria interactions using both pathogenic and carriage meningococcal isolates. Several pathogenic isolates of the ST-11 clonal complex and carriage isolates were used to infect human epithelial cells. Cytopathic effect was determined and apoptosis was scored using several methods (FITC-Annexin V staining followed by FACS analysis, caspase assays and DNA fragmentation). Only pathogenic isolates were able to induce apoptosis in human epithelial cells, mainly by lipooligosaccharide (endotoxin). Bioactive TNF-α is only detected when cells were infected by pathogenic isolates. At the opposite, carriage isolates seem to provoke shedding of the TNF-α receptor I (TNF-RI) from the surface that protect cells from apoptosis by chelating TNF-α. Ability to induce apoptosis and inflammation may represent major traits in the pathogenesis of N. meningitidis. However, our data strongly suggest that carriage isolates of meningococci reduce inflammatory response and apoptosis induction, resulting in the protection of their ecological niche at the human nasopharynx

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (1995). A tissue culture bilayer model to study the passage of Neisseria meningitidis.
  2. (1996). Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes.
  3. (2003). Apoptotic response of Chang cells to infection with Pseudomonas aeruginosa strains PAK and PAO-I: molecular ordering of the apoptosis signaling cascade and role of type IV pili.
  4. (2005). Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling.
  5. (1992). Bacterial meningitis: pathogenesis, pathophysiology, and progress.
  6. (2000). Carried meningococci in the Czech Republic: a diverse recombining population.
  7. (2003). Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38-2003. A 12-year-old girl with fever and coma.
  8. (2002). CD14-dependent activation of NF-kappaB by filarial parasitic sheath proteins.
  9. (1991). Cell death mechanisms and the immune system.
  10. (2005). Cross-talk between CD14 and complement receptor 3 promotes phagocytosis of mycobacteria: regulation by phosphatidylinositol 3-kinase and cytohesin-1.
  11. (1994). Cytokines in nasopharyngeal secretions; evidence for defective IL-1 beta production in children with recurrent episodes of acute otitis media.
  12. (2005). Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins.
  13. (1999). Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.
  14. (2004). Distribution of serogroups and genotypes among disease-associated and carried isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway.
  15. (2002). Downregulation of pili and capsule of Neisseria meningitidis upon contact with epithelial cells is mediated by CrgA regulatory protein.
  16. (2000). Effect of Chlamydia trachomatis infection and subsequent tumor necrosis factor alpha secretion on apoptosis in the murine genital tract.
  17. (2007). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis.
  18. (2003). Expression of proinflammatory cytokines and receptors by human fallopian tubes in organ culture following challenge with Neisseria gonorrhoeae.
  19. (1992). Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis.
  20. (2007). Gene expression pattern in human brain endothelial cells in response to Neisseria meningitidis.
  21. (2005). Genetic analysis of meningococci carried by children and young adults.
  22. (1999). Gonococcal infection of human fallopian tube mucosa in organ culture: relationship of mucosal tissue TNF-alpha concentration to sloughing of ciliated cells.
  23. (1988). Hemodynamic patterns of meningococcal shock in children.
  24. (1999). Host cell interactions and signalling with Neisseria gonorrhoeae.
  25. (2003). Host genetic determinants of Neisseria meningitidis infections.
  26. (2006). How Toll-like receptors signal: what we know and what we don’t know.
  27. (2008). Hyperinvasive genotypes of Neisseria meningitidis in France.
  28. (2001). Induction of epithelial cell death including apoptosis by enteropathogenic Escherichia coli expressing bundle-forming pili.
  29. (2006). Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis.
  30. (2003). Insertional inactivation of the lpxA gene involved in the biosynthesis of lipid A in Neisseria meningitidis resulted in lpxA/lpxA::aph-3’ heterodiploids.
  31. (2005). Lipooligosaccharide-independent alteration of cellular homeostasis in Neisseria meningitidis-infected epithelial cells.
  32. (1993). Mechanisms of endotoxin shock and endotoxin hypersensitivity.
  33. (1993). Meningococcal Opa and Opc proteins: their role in colonization and invasion of human epithelial and endothelial cells.
  34. (2006). Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling.
  35. (2004). Modulation of phagocyte apoptosis by bacterial pathogens.
  36. (2008). Molecular epidemiology of infectious diseases: the example of meningococcal disease.
  37. (2001). Molecular mechanisms of bacteria induced apoptosis.
  38. (1998). Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms.
  39. (1963). Neisseria Gonorrhoeae. I. Virulence Genetically Linked to Clonal Variation.
  40. (2002). Neisseria meningitidis can induce pro-inflammatory cytokine production via pathways independent from CD14 and toll-like receptor 4.
  41. (2000). Neisseria meningitidis induces the expression of the TNF-alpha gene in endothelial cells.
  42. (2004). Neisseria meningitidis lipooligosaccharide structure-dependent activation of the macrophage CD14/Toll-like receptor 4 pathway.
  43. (2001). Neisseria meningitidis lipopolysaccharides in human pathology.
  44. (2000). Neisseria meningitidis porin PorB interacts with mitochondria and protects cells from apoptosis.
  45. (1999). Neisserial porin (PorB) causes rapid calcium influx in target cells and induces apoptosis by the activation of cysteine proteases.
  46. (2005). Neisserial porin-induced dendritic cell activation is MyD88 and TLR2 dependent.
  47. (1992). Overexpression of metallothionein confers resistance to the cytotoxic effect of TNF with cadmium in MCF-7 breast carcinoma cells.
  48. (2002). Pathogenesis, Therapy, and Prevention of Meningococcal Sepsis.
  49. (1991). Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae.
  50. (1998). Pilusmediated adhesion of Neisseria meningitidis: the essential role of cell contactdependent transcriptional upregulation of the PilC1 protein.
  51. (2008). Reduced display of tumor necrosis factor receptor I at the host cell surface supports infection with Chlamydia trachomatis.
  52. (1991). Role of lipooligosaccharides in experimental dermal lesions caused by Haemophilus ducreyi.
  53. (1989). Soluble cytokine receptors are present in normal human urine.
  54. (1990). Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor.
  55. (2007). Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling.
  56. (2006). Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains.
  57. (1997). Structural features and biochemical properties of TNF-alpha converting enzyme (TACE).
  58. (2000). Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells.
  59. (1996). The influence of capsulation and lipooligosaccharide structure on neutrophil adhesion molecule expression and endothelial injury by Neisseria meningitidis.
  60. (2000). The modulation of host cell apoptosis by intracellular bacterial pathogens.
  61. (1991). The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells.
  62. (2001). The TNF and TNF receptor superfamilies: integrating mammalian biology.
  63. (1990). Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors.
  64. (1995). Two tumour necrosis factor receptors: structure and function.
  65. (2000). Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin Microbiol Rev 13: 144–166, table of contents.
  66. (2008). Wholegenome comparison of disease and carriage strains provides insights into virulence evolution in Neisseria meningitidis.
  67. (1999). Zychlinsky A

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.