title: A pathogenic trace of Tannerella forsythia - shedding of soluble fully active tumor necrosis factor α from the macrophage surface by karilysin.
abstract: Tannerella forsythia is implicated as a pathogen causing chronic and aggressive periodontitis. However, its virulence factors, including numerous putative proteases, are mostly uncharacterized. Karilysin is a newly described matrix metalloprotease-like enzyme of T. forsythia. Since pathogen-derived proteases may affect the host defense system via modulation of the cytokine network, the aim of this study was to determine the influence of karilysin on tumor necrosis factor-α (TNF-α). The results showed that karilysin cleaved the membrane form of TNF-α on the surface of macrophages, and that this led to an increased concentration of soluble TNF-α in the conditioned medium. Importantly, despite partial degradation of soluble TNF-α by karilysin, the released cytokine retained its biological activity, inducing apoptosis and stimulating autocrine pathway of pro-inflammatory gene expression. Notably, the observed effect required proteolytic activity by karilysin, since a catalytically inactive mutant of the enzyme did not affect TNF-α secretion. The shedding was independent of the activity of ADAM17, a major endogenous TNF-α converting enzyme. Karilysin-dependent TNF-α release from the cell surface is likely to occur in vivo because human plasma, the main constituent of gingival crevicular fluid, only slightly affected the sheddase activity of karilysin. Taken together, these results indicate that karilysin modulates the host immune response through regulation of TNF-α secretion, and should therefore be considered as a new virulence factor of T. forsythia.
authors.affiliation: Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Bryzek
authors.forename: M
authors.initials: M
authors.lastname: Ksiazek
authors.forename: E
authors.initials: E
authors.lastname: Bielecka
authors.forename: A Y
authors.initials: AY
authors.lastname: Karim
authors.forename: B
authors.initials: B
authors.lastname: Potempa
authors.forename: D
authors.initials: D
authors.lastname: Staniec
authors.forename: J
authors.initials: J
authors.lastname: Koziel
authors.forename: J
authors.initials: J
authors.lastname: Potempa
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D041963:Bacteroidetes / Q000201:enzymology / Q000472:pathogenicity*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D055550:Protein Stability; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; C572453:karilysin protein, Tannerella forsythia; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: Tannerella forsythia; karilysin; macrophages; periodontitis; tumor necrosis factor-α