Macrophages exposed to Borrelia burgdorferi induce Lyme arthritis in hamsters

Abstract

The mechanism(s) by which Lyme arthritis is induced has not been elucidated. In this study, we showed that macrophages have a direct, effector role in the pathogenesis of Lyme arthritis. Severe destructive arthritis was induced in recipients of macrophages obtained from Borrelia burgdorferi-vaccinated and nonvaccinated hamsters exposed to Formalin-inactivated B. burgdorferi in vitro and then challenged with the Lyme spirochete. Swelling of the hind paws was detected within 8 h of infection, increased rapidly, and peaked at 21 h. This initial swelling decreased, and by day 4 only slight swelling was detected. Severe swelling of the hind paws was detected 8 days after infection and increased rapidly, with peak swelling occurring on day 11. Histopathologic examination affirmed that macrophages exposed to Formalin-inactivated spirochetes induced a severe destructive Lyme arthritis. The onset and severity of the severe destructive arthritis were dependent on the number of macrophages transferred. By contrast, macrophages not exposed to Formalin-inactivated B. burgdorferi failed to induce severe destructive arthritis in recipients after challenge with B. burgdorferi. Similarly, severe destructive arthritis was not detected in recipients of macrophages injected with spirochetal growth medium. Our results also showed that transferred macrophages could not protect hamsters from infection with B. burgdorferi, as spirochetes were readily recovered from their tissues when cultured. These findings demonstrate that macrophages exposed to B. burgdorferi are directly involved in the induction of Lyme arthritis.

Macrophages interact with enriched populations of distinct T lymphocyte subsets for the induction of severe destructive Lyme arthritis

“…Control hamsters were injected subcutaneously in each hind paw with 0.4 mL of PBS without cells. We showed previously that hamsters inoculated with non-immune lymphocytes and macrophages did not induce SDLA [3]. In addition, vaccination of hamsters with Escherichia coli or Staphylococcus aureus in alum and then challenged with B. burgdorferi did not induce SDLA.…”

“…It is well established that T lymphocytes of the Th1 phenotype are involved in the activation of macrophages [29]. Macrophage activation, however, may be central to the induction of Lyme arthritis [3,4]. Elevated levels of various macrophage-derived molecules [interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E 2 , and collagenase] have been detected in synovial fluid extracts and serum from individuals with Lyme arthritis [30][31][32][33].…”

“…Giemsa-stained smears of isolated cells showed a homogeneous population of macrophages with no other types of leukocytes visible. We previously showed by flow cytometric analysis that preparations of macrophages obtained by this method were free of lymphocyte contamination [3].…”

“…Recently, we showed that macrophages play a direct effector role in the induction of Lyme arthritis [3]. Severe destructive arthritis was induced in recipient hamsters infused with macrophages from vaccinated or nonvaccinated hamsters exposed in vitro to formalin-inactivated B. burgdorferi (M-FBb) after infection with the Lyme borreliosis spirochete.…”

A joint effort: The interplay between the innate and the adaptive immune system in Lyme arthritis

“…In contrast, animals that received unprimed macrophages did not develop arthritis. 158 Furthermore, the combination of primed macrophages and T cells accelerated the development of arthritis in Borrelia-infected ICR mice compared to either one alone. 159,160 This highlights the impor-…”