Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis-Associated Locus 1 Is Dependent on Localized Differential Production of IFN- β and Requires Upregulation of Myostatin.

In this study, we show that mAb blockade revealed a unique role for IFN-β in Lyme arthritis development in B6.C3-Bbaa1 mice. Genetic control of IFN-β expression was also identified in bone marrow-derived macrophages stimulated with B. burgdorferi, and it was responsible for feed-forward amplification of IFN-stimulated genes. Reciprocal radiation chimeras between B6.C3-Bbaa1 and C57BL/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45(-) joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-β production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi. PMID: 28986440 [PubMed - as supplied by publisher]
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research

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In this study, we investigated the mechanisms that lead to the production of proinflammatory mediators by the murine macrophage cell line, RAW264.7, when these cells are exposed in vitro to recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). Using antibody protein microarray technology with high-throughput detection ability for detecting 25 chemokines in culture supernatant the RAW264.7 cell culture supernatants at 12 and 24 h post-stimulation with rBmpA, we identified two chemokines, a monocyte chemoattractant protein-5 (MCP-5/CCL12) and a macrophage inflammatory protein-2 (MIP-2/CXCL2), both of which incre...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
The study compares diagnostic parameters of different commercial serological kits based on three different antigen types and correlates test results with the status of the patient's Borrelia infection. In total, 8 IgM and 8 IgG kits were tested, as follows: enzyme-linked immunosorbent assay (ELISA) (Euroimmun) based on whole-cell antigen, 3 species-specific enzyme immunoassays (EIAs) (TestLine), Liaison chemiluminescence (DiaSorin), ELISA-Viditest (Vidia), EIA, and Blot-Line (TestLine) using recombinant antigens. All tests were performed on a panel of 90 samples from patients with clinically characterized borreliosis (53 w...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Immunoassays Source Type: research
Abstract Lyme disease (borreliosis) is a tick-borne bacterial infection caused by the spirochaete Borrelia burgdoferi, transmitted by hard-backed Ixodes ticks. Actual numbers of cases are increasing and it appears that the distribution across the UK is widening; however, it occurs most frequently in area of woodland, with temperate climate. It typically presents in mid to late summer. Lyme disease is a multisystem disease. The nervous system is the second most commonly affected system after the skin. Other systemic manifestations, such as carditis, keratitis, uveitis and inflammatory arthritis, rarely occur in Eur...
Source: Practical Neurology - Category: Neurology Authors: Tags: Pract Neurol Source Type: research
Cellular Microbiology,Volume 0, Issue ja, -Not available-.
Source: Cellular Microbiology - Category: Microbiology Authors: Source Type: research
As Lyme disease and Lyme arthritis spread to new regions in North America, physicians may ned to become aware of their signs and symptoms. Allen C. Steere, MD, says “Lyme arthritis is more complicated to treat than other manifestations of the disease.” Here are some best practices for treating Lyme arthritis...
Source: The Rheumatologist - Category: Rheumatology Authors: Tags: Conditions best practices Borrelia burgdorferi Lyme arthritis Lyme Disease Source Type: research
CONCLUSIONS: Our study provides insights into the alteration of the plasma phospholipid profile of LA patients, resulting from Borrelia burgdorferi infection, that may lead to improved LA diagnosis and differentiation of this disease from RA. Furthermore, LPE (14:0) was found to have a high potential to be a possible biomarker of LA. PMID: 30059653 [PubMed - as supplied by publisher]
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research
Given the variable clinical signs attributed to Borrelia burgdorferi, including infectious arthritis, neurologic disease, and behavioral changes, B burgdorferi is an important differential for decreased performance in sport horses. The primary vectors (Ixodes tick species) are expanding their range and thus Borrelia species are located in a wider area, making exposure more likely. Due to regionally high seroprevalence and vague clinical signs, diagnosis of Lyme disease in the horse is believed overestimated. Antibiotics are first-line treatment of confirmed Lyme disease. A single positive serologic test, by itself, is not ...
Source: Veterinary Clinics of North America: Equine Practice - Category: Veterinary Research Authors: Source Type: research
Host genotype influences the severity of murine Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi. C57BL/6 (B6) mice develop mild Lyme arthritis, whereas C3H/HeN (C3H) mice develop severe Lyme arthritis. Differential expression of interleukin 10 (IL-10) has long been associated with mouse strain differences in Lyme pathogenesis; however, the underlying mechanism(s) of this genotype-specific IL-10 regulation remained elusive. Herein we reveal a cAMP-mediated mechanism of IL-10 regulation in B6 macrophages that is substantially diminished in C3H macrophages. Under cAMP and CD14-p38 mitogen-activated ...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research
In the present study, we sought to evaluate the feasibility of targeting vascular adhesion protein-1 (VAP-1) by positron emission tomography (PET) for the longitudinal quantitative assessment of Borrelia burgdorf...
Source: Arthritis Research and Therapy - Category: Rheumatology Authors: Tags: Research article Source Type: research
Abstract The spirochete bacterium Borrelia burgdorferisensu lato is the causative agent of Lyme disease, the most common vector-borne disease in Europe and the United States. The spirochetes can be transmitted to humans via ticks, and then spread to different tissues, leading to arthritis, carditis and neuroborreliosis. Although antibiotics have commonly been used to treat infected individuals, some treated patients do not respond to antibiotics and experience persistent, long-term arthritis. Thus, there is a need to investigate alternative therapeutics against Lyme disease. The spirochete bacterium colonization i...
Source: Microbiology - Category: Microbiology Authors: Tags: Microbiology Source Type: research
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