Porphyromonas gingivalis Facilitates the Development and Progression of Destructive Arthritis through Its Unique Bacterial Peptidylarginine Deiminase (PAD)
Year: 2013
Type: article
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.
Source: PLoS Pathogens
Authors: Katarzyna J. Maresz, Annelie Hellvard, Aneta Sroka, Karina Adamowicz, Ewa Bielecka, Joanna Koziel, Katarzyna Gawron, Danuta Mizgalska, Katarzyna A. Marcinska, Malgorzata Benedyk, Krzysztof Pyrc, Anne-Marie Quirke, Roland Jonsson, Saba Alzabin, Patrick J. Venables, Ky-Anh Nguyen, Piotr Mydel, Jan Potempa
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: G2001484693, Rheumatoid Arthritis and Periodontal Inflammatory Disease (RAPID), BeTheCuRE, BACTERIAL PROTEINASES IN PERIODONTAL DISEASE, Determination of the role of P. gingivalis and P. intermedia proteases in mono- and synergistic mixed microbial infections in a mouse model of periodontal disease, G7264469277, Protein citrullination as a link between periodontal diseases and rheumatoid arthritis (RA) and target for development of novel drugs to treat RA
OpenAlex ID: W2061067592