A metalloproteinase karilysin present in the majority of Tannerella forsythia isolates inhibits all pathways of the complement system

Jusko, Monika; Potempa, Jan; Karim, Abdulkarim Y; Ksiazek, Miroslaw; Riesbeck, Kristian; Garred, Peter; Eick, Sigrun; Blom, Anna M (2012). A metalloproteinase karilysin present in the majority of Tannerella forsythia isolates inhibits all pathways of the complement system. Journal of immunology, 188(5), pp. 2338-49. Bethesda, Md.: American Association of Immunologists 10.4049/jimmunol.1101240

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology
UniBE Contributor:	Eick, Sigrun
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Language:	English
Submitter:	Eveline Carmen Schuler
Date Deposited:	04 Oct 2013 14:30
Last Modified:	05 Dec 2022 14:09
Publisher DOI:	10.4049/jimmunol.1101240
PubMed ID:	22287711
Web of Science ID:	000300610800034
URI:	https://boris.unibe.ch/id/eprint/11251 (FactScience: 217321)