Porphyromonas gingivalis Facilitates the Development and Progression of Destructive Arthritis through Its Unique Bacterial Peptidylarginine Deiminase (PAD)

PLoS Pathogens

Annelie Hellvard¹  Saba Alzabin¹  Malgorzata Benedyk²  Anne-Marie Quirke³  Katarzyna A. Marcinska³  Katarzyna J. Maresz³  Karina Adamowicz³  Katarzyna Gawron³  Ewa Bielecka³  Joanna Koziel³  Danuta Mizgalska³  Krzysztof Pyrc³  Jan Potempa⁴  Aneta Sroka⁵  Piotr Mydel⁶  Patrick J. Venables⁷  Roland Jonsson⁷  Ky-Anh Nguyen⁷ 

[1] Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway;Department of Human Developmental Biology, Jagiellonian University College of Medicine, Krakow, Poland;Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland;Department of Oral Biology, Faculty of Dentistry, University of Sydney, Sydney, Australia;Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Institute of Dental Research, Westmead Centre for Oral Health and Westmead Millennium Institute, Sydney, Australia;Kennedy Institute of Rheumatology, University of Oxford, London, United Kingdom

关键词: Arthritis;    Enzyme-linked immunoassays;    Rheumatoid arthritis;    Citrullination;    Antibodies;    Inoculation;    Inflammatory diseases;    Pathogens;   

DOI  :  10.1371/journal.ppat.1003627

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY