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A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System.

Jusko, Monika LU ; Potempa, Jan; Karim, Abdulkarim Y; Ksiazek, Miroslaw; Riesbeck, Kristian LU ; Garred, Peter; Eick, Sigrun and Blom, Anna LU (2012) In Journal of immunology (Baltimore, Md. : 1950) 188(5). p.2338-2349
Abstract
Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways, T. forsythia is resistant to killing by human complement, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with karilysin, a metalloproteinase of T. forsythia, resulted in a decrease in bactericidal activity of the serum. T. forsythia strains expressing karilysin at higher levels were more resistant than low-expressing strains. Furthermore, the low-expressing strain was significantly more opsonized with activated complement factor 3 and... (More)
Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways, T. forsythia is resistant to killing by human complement, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with karilysin, a metalloproteinase of T. forsythia, resulted in a decrease in bactericidal activity of the serum. T. forsythia strains expressing karilysin at higher levels were more resistant than low-expressing strains. Furthermore, the low-expressing strain was significantly more opsonized with activated complement factor 3 and membrane attack complex from serum compared with the other strains. The high-expressing strain was more resistant to killing in human blood. The protective effect of karilysin against serum bactericidal activity was attributable to its ability to inhibit complement at several stages. The classical and lectin complement pathways were inhibited because of the efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4 by karilysin, whereas inhibition of the terminal pathway was caused by degradation of C5. Interestingly, karilysin was able to release biologically active C5a peptide in human plasma and induce migration of neutrophils. Importantly, we detected the karilysin gene in >90% of gingival crevicular fluid samples containing T. forsythia obtained from patients with periodontitis. Taken together, the newly characterized karilysin appears to be an important virulence factor of T. forsythia and might have several important implications for immune evasion. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
188
issue
5
pages
2338 - 2349
publisher
American Association of Immunologists
external identifiers
  • wos:000300610800034
  • pmid:22287711
  • scopus:84857463226
ISSN
1550-6606
DOI
10.4049/jimmunol.1101240
language
English
LU publication?
yes
id
da67e771-3165-45da-927a-217931853318 (old id 2335911)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22287711?dopt=Abstract
date added to LUP
2012-02-01 21:30:47
date last changed
2017-08-13 04:42:31
@article{da67e771-3165-45da-927a-217931853318,
  abstract     = {Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways, T. forsythia is resistant to killing by human complement, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with karilysin, a metalloproteinase of T. forsythia, resulted in a decrease in bactericidal activity of the serum. T. forsythia strains expressing karilysin at higher levels were more resistant than low-expressing strains. Furthermore, the low-expressing strain was significantly more opsonized with activated complement factor 3 and membrane attack complex from serum compared with the other strains. The high-expressing strain was more resistant to killing in human blood. The protective effect of karilysin against serum bactericidal activity was attributable to its ability to inhibit complement at several stages. The classical and lectin complement pathways were inhibited because of the efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4 by karilysin, whereas inhibition of the terminal pathway was caused by degradation of C5. Interestingly, karilysin was able to release biologically active C5a peptide in human plasma and induce migration of neutrophils. Importantly, we detected the karilysin gene in >90% of gingival crevicular fluid samples containing T. forsythia obtained from patients with periodontitis. Taken together, the newly characterized karilysin appears to be an important virulence factor of T. forsythia and might have several important implications for immune evasion.},
  author       = {Jusko, Monika and Potempa, Jan and Karim, Abdulkarim Y and Ksiazek, Miroslaw and Riesbeck, Kristian and Garred, Peter and Eick, Sigrun and Blom, Anna},
  issn         = {1550-6606},
  language     = {eng},
  number       = {5},
  pages        = {2338--2349},
  publisher    = {American Association of Immunologists},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1101240},
  volume       = {188},
  year         = {2012},
}