Dataset Information

Lyme arthritis resolution with antiserum to a 37-kilodalton Borrelia burgdorferi protein.

ABSTRACT: A 37-kDa protein from Borrelia burgdorferi (the agent of Lyme disease) was identified as a target for immune-mediated resolution of Lyme arthritis. Studies in a mouse model have shown that arthritis resolution can be mediated by antibodies (against unknown target antigens) within immune sera from actively infected mice. Immune sera from infected mice were therefore used to screen a B. burgdorferi genomic expression library. A gene was identified whose native product is a putative lipoprotein of approximately 37 kDa, referred to here as arthritis-related protein (Arp). Active and passive immunization of mice with recombinant Arp or Arp antiserum, respectively, did not protect mice from challenge inoculation. However, when Arp antiserum was administered to severe combined immunodeficient (SCID) mice with established infections and with ongoing arthritis and carditis, treatment selectively induced arthritis resolution without affecting the status of carditis or influencing the status of infection, including spirochetemia. The selective arthritis-resolving effect of Arp antiserum mimics the activity of immune serum from immunocompetent mice when such serum is transferred into SCID mice with established infections. The arp gene could not be amplified from unrelated B. burgdorferi isolates but hybridized with those isolates only under very-low-stringency conditions. Arp antiserum reacted against proteins of similar size in a wide range of B. burgdorferi isolates.

SUBMITTER: Feng S

PROVIDER: S-EPMC101718 | biostudies-literature | 2000 Jul

REPOSITORIES: biostudies-literature

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Lyme arthritis resolution with antiserum to a 37-kilodalton Borrelia burgdorferi protein.

Feng S S Hodzic E E Barthold S W SW

Infection and immunity 20000701 7

A 37-kDa protein from Borrelia burgdorferi (the agent of Lyme disease) was identified as a target for immune-mediated resolution of Lyme arthritis. Studies in a mouse model have shown that arthritis resolution can be mediated by antibodies (against unknown target antigens) within immune sera from actively infected mice. Immune sera from infected mice were therefore used to screen a B. burgdorferi genomic expression library. A gene was identified whose native product is a putative lipoprotein of ...[more]

PMID: 10858233

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Project description:MicroRNAs have been shown to be important regulators of inflammatory and immune responses and are implicated in several immune disorders including systemic lupus erythematosus and rheumatoid arthritis, but their role in Lyme borreliosis remains unknown. We performed a microarray screen for expression of miRNAs in joint tissue from three mouse strains infected with Borrelia burgdorferi. This screen identified upregulation of miR-146a, a key negative regulator of NF-κB signaling, in all three strains, suggesting it plays an important role in the in vivo response to B. burgdorferi. Infection of B6 miR-146a-/- mice with B. burgdorferi revealed a critical nonredundant role of miR-146a in modulating Lyme arthritis without compromising host immune response or heart inflammation. The impact of miR-146a was specifically localized to the joint, and did not impact lesion development or inflammation in the heart. Furthermore, B6 miR-146a-/- mice had elevated levels of NF-κB-regulated products in joint tissue and serum late in infection. Flow cytometry analysis of various lineages isolated from infected joint tissue of mice showed that myeloid cell infiltration was significantly greater in B6 miR-146a-/- mice, compared to B6, during B. burgdorferi infection. Using bone marrow-derived macrophages, we found that TRAF6, a known target of miR-146a involved in NF-κB activation, was dysregulated in resting and B. burgdorferi-stimulated B6 miR-146a-/- macrophages, and corresponded to elevated IL-1β, IL-6 and CXCL1 production. This dysregulated protein production was also observed in macrophages treated with IL-10 prior to B. burgdorferi stimulation. Peritoneal macrophages from B6 miR-146a-/- mice also showed enhanced phagocytosis of B. burgdorferi. Together, these data show that miR-146a-mediated regulation of TRAF6 and NF-κB, and downstream targets such as IL-1β, IL-6 and CXCL1, are critical for modulation of Lyme arthritis during chronic infection with B. burgdorferi.

Dataset Information

Lyme arthritis resolution with antiserum to a 37-kilodalton Borrelia burgdorferi protein.

Publications

Lyme arthritis resolution with antiserum to a 37-kilodalton Borrelia burgdorferi protein.

Similar Datasets

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