Our laboratory and others have used the C3H mouse model of Lyme borreliosis to evaluate whether viable B. ![]() Adaptive immunity is required for resolution of joint inflammation, which usually occurs within 45–60 days of infection even though spirochetes persist in tissues throughout the life span of the mouse ( 5, 8, 10). burgdorferi via TLRs, as demonstrated by the markedly elevated pathogen burdens in mice deficient in B cells, in TLR2, or in the TLR intracellular adaptor molecule myeloid differentiation antigen 88 (MyD88) ( 8– 11). Effective pathogen control requires both specific Ab production and phagocyte recognition of B. Strain differences in disease susceptibility are influenced by both hematopoietic and nonhematopoietic factors and are preserved in SCID mice that lack functional T and B cells ( 6, 7). Disease severity is mouse strain dependent, with C3H mice more susceptible than C57BL/6 (B6) mice. All laboratory mice are susceptible to infection and develop subacute arthritis and myocarditis similar to that of humans infected with B. The mouse model of Lyme borreliosis has provided a useful system for studying B. The pathogenic mechanisms underlying the delay in symptom resolution after treatment for early disease and the persistence of objective late signs such as arthritis are incompletely defined. burgdorferi is difficult to detect by culture except in early infection when EM is present ( 4). Although ongoing infection is considered an unlikely explanation for persistent symptoms or disease, it cannot be definitively excluded because B. Patients who present with the late-stage manifestation of arthritis may evolve persistent joint inflammation that no longer responds to antibiotics ( 3). Although the disease is responsive to antibiotics, up to 25% of patients treated early in the course of infection can experience protracted musculoskeletal symptoms of unclear etiology ( 2). ![]() Spirochetes deposited in the skin during tick feeding can cause the localized skin rash erythema migrans (EM) or disseminate to cause disease mainly involving other areas of the skin and/or the heart, joints, and nervous system. Lyme disease is an emerging zoonotic infection caused by the Ixodes tick–transmitted spirochete Borrelia burgdorferi ( 1). We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. This is the first direct demonstration that inflammatory B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. 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. ![]() 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. ![]() 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. 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.
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