Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis

Simple item page
dc.contributor.authorJutras, Brandon L.en
dc.contributor.authorLochhead, Robert B.en
dc.contributor.authorKloos, Zachary A.en
dc.contributor.authorBiboy, Jacoben
dc.contributor.authorStrle, Klemenen
dc.contributor.authorBooth, Carmen J.en
dc.contributor.authorGovers, Sander K.en
dc.contributor.authorGray, Joeen
dc.contributor.authorSchumann, Peteren
dc.contributor.authorVollmer, Waldemaren
dc.contributor.authorBockenstedt, Linda K.en
dc.contributor.authorSteere, Allen C.en
dc.contributor.authorJacobs-Wagner, Christineen
dc.contributor.departmentBiochemistryen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2019-06-18T14:46:52Zen
dc.date.available2019-06-18T14:46:52Zen
dc.date.issued2019-06-17en
dc.description.abstractLyme 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.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1073/pnas.1904170116en
dc.identifier.urihttp://hdl.handle.net/10919/90228en
dc.language.isoenen
dc.publisherNational Academy of Sciencesen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectLyme diseaseen
dc.subjectarthritisen
dc.subjectpeptidoglycanen
dc.subjectBorrelia burgdorferien
dc.subjectinflammationen
dc.titleBorrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritisen
dc.title.serialProceedings of the National Academy of Sciencesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1904170116.full.pdf
Size:
1.18 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
Name:
license.txt
Size:
1.5 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Scholarly Works, Fralin Life Sciences Institute
Scholarly Works, Biochemistry