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.
Read more here:
http://www.jci.org/articles/view/58813
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