Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A 2019 Jul 02;116(27):13498-13507
Date
06/19/2019Pubmed ID
31209025Pubmed Central ID
PMC6613144DOI
10.1073/pnas.1904170116Scopus ID
2-s2.0-85068263050 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
Lyme disease is a multisystem disorder caused by the spirochete Borrelia burgdorferi A common late-stage complication of this disease is oligoarticular arthritis, often involving the knee. In ∼10% of cases, arthritis persists after appropriate antibiotic treatment, leading to a proliferative synovitis typical of chronic inflammatory arthritides. Here, we provide evidence that peptidoglycan (PG), a major component of the B. burgdorferi cell envelope, may contribute to the development and persistence of Lyme arthritis (LA). We show that B. burgdorferi has a chemically atypical PG (PGBb) that is not recycled during cell-wall turnover. Instead, this pathogen sheds PGBb fragments into its environment during growth. Patients with LA mount a specific immunoglobulin G response against PGBb, which is significantly higher in the synovial fluid than in the serum of the same patient. We also detect PGBb in 94% of synovial fluid samples (32 of 34) from patients with LA, many of whom had undergone oral and intravenous antibiotic treatment. These same synovial fluid samples contain proinflammatory cytokines, similar to those produced by human peripheral blood mononuclear cells stimulated with PGBb In addition, systemic administration of PGBb in BALB/c mice elicits acute arthritis. Altogether, our study identifies PGBb as a likely contributor to inflammatory responses in LA. Persistence of this antigen in the joint may contribute to synovitis after antibiotics eradicate the pathogen. Furthermore, our finding that B. burgdorferi sheds immunogenic PGBb fragments during growth suggests a potential role for PGBb in the immunopathogenesis of other Lyme disease manifestations.
Author List
Jutras BL, Lochhead RB, Kloos ZA, Biboy J, Strle K, Booth CJ, Govers SK, Gray J, Schumann P, Vollmer W, Bockenstedt LK, Steere AC, Jacobs-Wagner CAuthor
Robert Lochhead PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptive ImmunityAnimals
Antigens, Bacterial
Borrelia burgdorferi
Cytokines
Female
Humans
Lyme Disease
Mice
Mice, Inbred BALB C
Peptidoglycan
Synovial Fluid