Posttreatment Chronic Lyme Disease—What It Is Not

Radolf, Justin D.

doi:10.1086/432736

Cited by 13 publications

(7 citation statements)

References 20 publications

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“…However, 10–20% of patients present with persistent arthritis for months or years after standard antibiotic regimen, referred to as antibiotic-refractory arthritis or post-treatment Lyme disease (PTLD)(4, 5). Patients are negative for the presence of B. burgdorferi DNA after standard antibiotic therapy, raising several questions regarding the etiology of this long-lasting illness (6–8). Persistent Lyme arthritis shares certain pathogenic themes with rheumatoid arthritis such as similar synovial lesions, a dominant T-helper 1 (Th1) CD4 + T cell response in synovial tissues, and high concentrations of pro-inflammatory chemoattractants for CD4 + and CD8 + T cells in synovial fluid (9–11).…”

Section: Introductionmentioning

confidence: 99%

IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis

Whiteside

Snook

et al. 2018

The Journal of Immunology

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T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4 and CD8 T cells leads to arthritis-promoting IFN-γ, similar to the inflammatory environment seen in the synovial tissue of patients with posttreatment Lyme disease. TCR transgenic mice containing monoclonal specificity toward non- epitopes confirmed that bystander T cell activation was responsible for disease development. The microbial pattern recognition receptor TLR2 was upregulated on T cells following infection, implicating it as marker of bystander T cell activation. In fact, T cell-intrinsic expression of TLR2 contributed to IFN-γ production and arthritis, providing a mechanism for microbial-induced bystander T cell activation during infection. The IL-10-deficient mouse reveals a novel TLR2-intrinsic role for T cells in Lyme arthritis, with potentially broad application to immune pathogenesis.

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Section: Introductionmentioning

confidence: 99%

IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis

Whiteside

Snook

et al. 2018

The Journal of Immunology

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“…While B. burgdorferi persists in several tissue locations in mammals, only a limited set of organs, most frequently the joints and the heart, experience robust host-inflammatory responses resulting in clinical complications, such as Lyme arthritis and carditis. Antibiotic treatment is usually, but not always, successful, and some patients develop a form of antibiotic-resistant arthritis that is thought to be unrelated to persistent infection [4].…”

Section: Introductionmentioning

confidence: 99%

A Chromosomally Encoded Virulence Factor Protects the Lyme Disease Pathogen against Host-Adaptive Immunity

et al. 2009

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Borrelia burgdorferi, the bacterial pathogen of Lyme borreliosis, differentially expresses select genes in vivo, likely contributing to microbial persistence and disease. Expression analysis of spirochete genes encoding potential membrane proteins showed that surface-located membrane protein 1 (lmp1) transcripts were expressed at high levels in the infected murine heart, especially during early stages of infection. Mice and humans with diagnosed Lyme borreliosis also developed antibodies against Lmp1. Deletion of lmp1 severely impaired the pathogen's ability to persist in diverse murine tissues including the heart, and to induce disease, which was restored upon chromosomal complementation of the mutant with the lmp1 gene. Lmp1 performs an immune-related rather than a metabolic function, as its deletion did not affect microbial persistence in immunodeficient mice, but significantly decreased spirochete resistance to the borreliacidal effects of anti-B. burgdorferi sera in a complement-independent manner. These data demonstrate the existence of a virulence factor that helps the pathogen evade host-acquired immune defense and establish persistent infection in mammals.

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“…Lyme arthritis occurs in a substantial number of untreated patients ( 1 ), often several weeks to months after the tick bite, and is associated with spirochete invasion of the joints ( 3 ). In most cases, antibiotic therapy is curative; however, some patients develop a form of antibiotic-resistant arthritis that is thought to be unrelated to persistent infection ( 5 ).…”

mentioning

confidence: 99%

Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis

Pal

Wang

Bao

et al. 2007

The Journal of Experimental Medicine

108

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Lyme arthritis results from colonization of joints by Borrelia burgdorferi and the ensuing host response. Using gene array–based differential analysis of B. burgdorferi gene expression and quantitative reverse trancription-polymerase chain reaction, we identified two paralogous spirochete genes, bmpA and bmpB, that are preferentially up-regulated in mouse joints compared with other organs. Transfer of affinity-purified antibodies against either BmpA or BmpB into B. burgdorferi–infected mice selectively reduced spirochete numbers and inflammation in the joints. B. burgdorferi lacking bmpA/B were therefore generated to further explore the role of these proteins in the pathogenesis of Lyme disease. B. burgdorferi lacking bmpA/B were infectious in mice, but unable to persist in the joints, and they failed to induce severe arthritis. Complementation of the mutant spirochetes with a wild-type copy of the bmpA and bmpB genes partially restored the original phenotype. These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis.

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Posttreatment Chronic Lyme Disease—What It Is Not

Cited by 13 publications

References 20 publications

IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis

IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis

A Chromosomally Encoded Virulence Factor Protects the Lyme Disease Pathogen against Host-Adaptive Immunity

Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis

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