Differential modulation of TNF-alpha-induced apoptosis by Neisseria meningitidis.
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.
Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France. ala-eddine.deghmane@pasteur.fr
Ala-Eddine
AE
Deghmane
Carole
C
Veckerlé
Dario
D
Giorgini
Eva
E
Hong
Corinne
C
Ruckly
Muhamed-Kheir
MK
Taha
D000704:Analysis of Variance; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D002353:Carrier State / Q000382:microbiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004731:Endotoxins / Q000378:metabolism; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008589:Meningococcal Infections / Q000382:microbiology*; D008856:Microscopy, Fluorescence; D009345:Neisseria meningitidis / Q000378:metabolism / Q000472:pathogenicity*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001426:Bacterial Proteins; D004731:Endotoxins; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha