Journal article
Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD).
- Abstract:
- Rheumatoid arthritis and periodontitis are two prevalent chronic inflammatory diseases in humans and are associated with each other both clinically and epidemiologically. Recent findings suggest a causative link between periodontal infection and rheumatoid arthritis via bacteria-dependent induction of a pathogenic autoimmune response to citrullinated epitopes. Here we showed that infection with viable periodontal pathogen Porphyromonas gingivalis strain W83 exacerbated collagen-induced arthritis (CIA) in a mouse model, as manifested by earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction. The ability of P. gingivalis to augment CIA was dependent on the expression of a unique P. gingivalis peptidylarginine deiminase (PPAD), which converts arginine residues in proteins to citrulline. Infection with wild type P. gingivalis was responsible for significantly increased levels of autoantibodies to collagen type II and citrullinated epitopes as a PPAD-null mutant did not elicit similar host response. High level of citrullinated proteins was also detected at the site of infection with wild-type P. gingivalis. Together, these results suggest bacterial PAD as the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 834.2KB, Terms of use)
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- Publisher copy:
- 10.1371/journal.ppat.1003627
Authors
+ Innovative Medicines Initiative Joint Undertaking
More from this funder
- Funding agency for:
- Venables, P
- Grant:
- 115142-2
+ Imperial National Institute of Health Research
More from this funder
- Funding agency for:
- Venables, P
- Grant:
- 115142-2
- Publisher:
- Public Library of Science
- Journal:
- PLoS pathogens More from this journal
- Volume:
- 9
- Issue:
- 9
- Pages:
- e1003627
- Publication date:
- 2013-09-01
- DOI:
- EISSN:
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1553-7374
- ISSN:
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1553-7366
- Language:
-
English
- UUID:
-
uuid:df66264e-dd94-4d25-a08a-2dd65cf63cff
- Local pid:
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pubs:431371
- Source identifiers:
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431371
- Deposit date:
-
2013-11-16
Terms of use
- Copyright holder:
- Maresz et al
- Copyright date:
- 2013
- Notes:
- © 2013 Maresz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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