Disease severity in a murine model of lyme borreliosis is associated with the genotype of the infecting Borrelia burgdorferi sensu stricto strain.
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The pathogenicity of Borrelia burgdorferi sensu stricto clinical isolates representing 2 distinct ribosomal DNA spacer restriction fragment-length polymorphism genotypes (RSTs) was assessed in a murine model of Lyme disease. B. burgdorferi was recovered from 71.5% and 26.6% of specimens from mice infected with RST1 and RST3 isolates, respectively (P<.0001). The average ankle diameter and histologic scores for carditis and arthritis were significantly higher after 2 weeks of infection among mice infected with RST1 isolates than among those infected with RST3 isolates (P<.001). These clinical manifestations were associated with larger numbers of spirochetes in target tissues but not with the serum sensitivity of the individual isolates. Thus, the development and severity of disease in genetically identical susceptible hosts is determined mainly by the pathogenic properties of the infecting B. burgdorferi isolate. The RST1 genotype is genetically homogeneous and thus may represent a recently evolved clonal lineage that is highly pathogenic in humans and animals. (+info)
An OspA-based genospecies identification of Lyme disease spirochetes (Borrelia burgdorferi) isolated in Taiwan.
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To further identify the genospecies of Lyme disease spirochetes (Borrelia burgdorferi) isolated in Taiwan, we analyzed the genomic identities of these Taiwan isolates (TWKM1-7) by genospecies-specific polymerase chain reaction (PCR) assay, restriction fragment length polymorphism (RFLP) analysis, and gene sequencing based on the OspA gene sequences of B. burgdorferi sensu lato. PCR analysis indicates that all of these Taiwan isolates were genetically related to the genospecies of B. burgdorferi sensu stricto by their differential reactivities with genospecies-specific PCR primers. After cleavage by DraI, three different RFLP patterns in relation to three different genospecies of Lyme disease spirochetes were observed, and all of these Taiwan isolates were affiliated with the genospecies of B. burgdorferi sensu stricto. The phylogenetic analysis also reveals that the sequence similarity of PCR-amplified OspA gene of these Taiwan isolates is highly homogeneous, with a homogeneity of more than 99.8% within the genospecies of B. burgdorferi sensu stricto. These results confirm that the genomic identities of these Taiwan isolates belong to the genospecies of B. burgdorferi sensu stricto. (+info)
Chemotactic migration of the Lyme disease spirochete (Borrelia burgdorferi) to salivary gland extracts of vector ticks.
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The migration of Lyme disease spirochetes (Borrelia burgdorferi) toward salivary gland extracts (SGEs) of vector ticks was determined by a modified U-tube chemotaxis assay. Responses of cultured spirochetes to the SGEs were measured by dark-field microscopy at intervals after the initial inoculation. The average numbers of spirochetes that migrated were compared between U-tubes containing either SGEs or phosphate-buffered saline (PBS). Spirochetes showed increased migration in tubes containing SGE, and migration was approximately 10-20-fold higher than that for spirochetes observed in tubes containing PBS. In addition, the span of migration showed no significant difference relative to the origin of spirochete isolation. These results demonstrate that spirochete migration can be enhanced by SGEs from fed vector ticks. This mechanism may contribute to the novel transmission of Lyme disease spirochetes between cofeeding infected and uninfected ticks in nature. (+info)
Gamma interferon inhibits production of Anti-OspA borreliacidal antibody in vitro.
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The ability of a Lyme borreliosis vaccine to induce and maintain sustained levels of borreliacidal antibody is necessary for prolonged protection against infection with Borrelia burgdorferi. Vaccination against infection with B. burgdorferi could be improved by determining the mechanism(s) that influences the production of protective borreliacidal antibody. Borreliacidal antibody was inhibited in cultures of lymph node cells obtained from C3H/HeJ mice vaccinated with formalin-inactivated B. burgdorferi and cultured with macrophages and B. burgdorferi and treated with recombinant gamma interferon (rIFN-gamma). The suppression of production of outer surface protein A (OspA) borreliacidal antibody by rIFN-gamma was not affected by the time of treatment. In addition, treatment with rIFN-gamma inhibited the production of other anti-B. burgdorferi antibodies. By contrast, treatment of cultures of immune lymph node cells with anti-IFN-gamma marginally increased the production of borreliacidal antibody and enhanced the production of other antibodies directed against B. burgdorferi. These results show that IFN-gamma does not play a major role in the production of anti-OspA borreliacidal antibody. Additional studies are needed to determine which cytokine(s) will enhance production of borreliacidal antibody. (+info)
Detection of four Borrelia burgdorferi genospecies and first report of human granulocytic ehrlichiosis agent in Ixodes ricinus ticks collected in central Italy.
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The presence of Borrelia burgdorferi s.l. and of Ehrlichia phagocytophila group was sought by PCR in Ixodes ricinus collected in a protected area of central Italy. Nymphs (n = 1475, gathered in 295 pools of 5 nymphs each) and adult ticks (n = 28) were examined. B. burgdorferi s.l. was detected in 13.8% of the nymph pools; of these, 63.4% were infected by B. valaisiana, 26.8% by B. afzelii, 7.3% by B. garinii, and 2.5% by B. burgdorferi s.s. Only a single adult male tick proved to host B. afzelii. The agent of human granulocytic ehrlichiosis (HGE) was detected in 2.7% of the nymph pools. Two HGE agent-positive nymph pools were also found to be positive for B. garinii and for B. afzelii, respectively. This is the first report from central Italy of the finding of the HGE agent in ticks. (+info)
Interleukin-10 inhibits proinflammatory activation of endothelium in response to Borrelia burgdorferi or lipopolysaccharide but not interleukin-1beta or tumor necrosis factor alpha.
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Interleukin (IL)-10 is generally regarded as an anti-inflammatory cytokine, since it acts on a variety of cell types to suppress production of proinflammatory mediators. In inflammation, endothelial cells (EC) play a crucial role in recruiting leukocytes to sites of injury or infection. In this study, the actions of IL-10 on human umbilical vein EC were investigated. IL-10 reduced migration of monocytes and T lymphocytes across endothelium stimulated by lipopolysaccharide and decreased endothelial production of chemokines in response to lipopolysaccharide and Borrelia burgdorferi, the agent of Lyme disease. However, IL-10 did not affect these responses when EC were activated by the host proinflammatory cytokines IL-lbeta or tumor necrosis factor alpha. Moreover, IL-10 did not prevent up-regulation of the adhesion molecules E-selectin and intercellular adhesion molecule-1 by EC exposed to any of these activating agents. IL-10 therefore inhibits proinflammatory activation of EC in a manner that is selective with respect to stimulus and effector response. (+info)
Differential survival of Lyme borreliosis spirochetes in ticks that feed on birds.
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The abilities of the most common European genospecies of Borrelia burgdorferi sensu lato to survive blood meals taken by ticks feeding on birds were analyzed. A pattern of differential survival of the spirochetes in feeding ticks was observed. The result is consistent with the concept of selective transmission of Lyme borreliosis spirochetes. (+info)
The responsiveness of human V delta 1 gamma delta T cells to Borrelia burgdorferi is largely restricted to synovial-fluid cells from patients with Lyme arthritis.
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It has been shown that human gamma delta T cells expressing the V delta 1 T cell receptor (TCR) respond to the spirochete Borrelia burgdorferi. Lysates of 3 Borrelia genospecies triggered the proliferation of peripheral-blood mononuclear cells not only from patients with skin manifestations of Borrelia infection and from patients with Lyme arthritis but also from healthy donors. However, with the exception of 1 patient with Lyme arthritis, no selective expansion of V delta 1-expressing gamma delta T cells was induced. In contrast, synovial-fluid mononuclear cells (SFMC) from 3 of 5 patients with Lyme arthritis responded with a selective outgrowth of V delta 1 gamma delta T cells. V delta 1 gamma delta T cell lines established from SFMC coexpressed various TCR V gamma chains, although V gamma 8 was preferentially used. Thus, the responsiveness to Borrelia antigens is not a general property of V delta 1-expressing gamma delta T cells but is largely restricted to V delta 1 gamma delta T cells recruited into the inflamed tissue. (+info)