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Published on: July 17, 2016
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
Abstract:
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-alpha is only detected when cells were infected by pathogenic isolates. At the opposite, carriage isolates seem to provoke shedding of the TNF-alpha receptor I (TNF-RI) from the surface that protect cells from apoptosis by chelating TNF-alpha. 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.
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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