Journal Article

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

Jonsson, Roland, Mizgalska, Danuta, Sroka, Aneta, Gawron, Katarzyna, Potempa, Jan, Maresz, Katarzyna J., Pyrc, Krzysztof, Bielecka, Ewa, Alzabin, Saba, Benedyk, Malgorzata, Hellvard, Annelie, Koziel, Joanna, Venables, Patrick J., Adamowicz, Karina, Quirke, Anne-Marie, Nguyen, Ky-Anh, Mydel, Piotr, Marcinska, Katarzyna A.

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACTIVE RHEUMATOID-ARTHRITIS / ALPHA-ENOLASE / Animals / Arthritis - immunology / Arthritis - microbiology / Arthritis - pathology / Arthritis - physiopathology / AUTOANTIBODIES / Autoantibodies - analysis / AUTOIMMUNITY / Bacteria / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Bacteroidaceae Infections - immunology / Bacteroidaceae Infections - microbiology / Bacteroidaceae Infections - pathology / Bacteroidaceae Infections - physiopathology / Biomedical research / Bone Resorption - etiology / Chronic obstructive pulmonary disease / CITRULLINATED PROTEINS / Citrulline - metabolism / Clinical Medicine / Collagen / Development and progression / Disease Models, Animal / Disease Progression / Drug therapy / Gene Deletion / Gram-negative bacteria / Health aspects / Host-parasite relationships / Hydrolases - genetics / Hydrolases - metabolism / Immune system / Infections / Joints - immunology / Joints - metabolism / Joints - microbiology / Joints - pathology / Klinisk medicin / Laboratory animals / Male / Medical research / Mice, Inbred DBA / Neutrophil Infiltration / PERIODONTAL-DISEASE / Periodontitis - immunology / Periodontitis - metabolism / Periodontitis - microbiology / Periodontitis - pathology / Physiological aspects / Porphyromonas gingivalis - enzymology / Porphyromonas gingivalis - immunology / Porphyromonas gingivalis - isolation & purification / POSTTRANSLATIONAL MODIFICATIONS / Prevotella intermedia - enzymology / Prevotella intermedia - immunology / Prevotella intermedia - isolation & purification / PREVOTELLA-INTERMEDIA / Protein Processing, Post-Translational / Protein-Arginine Deiminases / Proteins / Rheumatoid arthritis / SEVERITY / Severity of Illness Index / SIGNALING PATHWAYS