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Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy
- Source :
- The Journal of clinical investigation. 122(7)
- Publication Year :
- 2011
-
Abstract
- An enigmatic feature of Lyme disease is the slow resolution of musculoskeletal symptoms that can continue after treatment, with some patients developing an inflammatory arthritis that becomes refractory to antibiotic therapy. Using intravital microscopy and the mouse model of Lyme borreliosis, we observed that Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment. B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice and all but one of the immunodeficient mice with heightened pathogen burden due to impaired TLR responsiveness. Amorphous GFP+ deposits were visualized by intravital microscopy in the entheses of antibiotic-treated mice infected with GFP-expressing spirochetes and on the ear cartilage surface in sites where immunofluorescence staining detected spirochete antigens. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis.
- Subjects :
- Green Fluorescent Proteins
Arthritis
Lyme Arthritis
Mice
Lyme disease
medicine
Animals
Borrelia burgdorferi
Ear, External
Doxycycline
Mice, Knockout
Antigens, Bacterial
Arthritis, Infectious
Lyme Disease
Mice, Inbred C3H
biology
Ceftriaxone
General Medicine
Patella
bacterial infections and mycoses
biology.organism_classification
medicine.disease
Bacterial Load
Recombinant Proteins
Anti-Bacterial Agents
Mice, Inbred C57BL
Cartilage
Microscopy, Fluorescence, Multiphoton
Immunology
Myeloid Differentiation Factor 88
Lyme disease microbiology
Female
Intravital microscopy
Xenodiagnosis
Joint Capsule
Research Article
medicine.drug
Fluorescence Recovery After Photobleaching
Subjects
Details
- ISSN :
- 15588238
- Volume :
- 122
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical investigation
- Accession number :
- edsair.doi.dedup.....b2dcc6517459135623d4d5c65ce66c83