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Published on: July 15, 2011
Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever
V Vidal1, I G Scragg, S J Cutler
1University Department of Pediatrics, Oxford University, United Kingdom.
Abstract:
Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce tumor necrosis factor. We show that the predominant factor inducing tumor necrosis factor is a variable lipoprotein homologous to the variable major protein of B. hermsii. We found antibodies to different forms of variable major protein in two patients with louse-borne relapsing fever. The three purified variable major proteins studied here differ in their ability to induce tumor necrosis factor production, which may partly explain the variable clinical severity of borrelial infection. These results may be of considerable relevance for the pathogenesis of Lyme disease and other forms of human borreliosis.
Insights
Antibiotic treatment for relapsing fever can cause a dangerous reaction due to tumor necrosis factor release. Researchers identified a specific Borrelia recurrentis lipoprotein as the main trigger, offering insights into disease severity and Lyme disease.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Relapsing fever caused by Borrelia recurrentis can lead to severe Jarisch-Herxheimer reactions after antibiotic treatment.
- Tumor necrosis factor (TNF) release is implicated in the pathogenesis of these reactions.
- Understanding the specific bacterial components triggering TNF is crucial for managing borreliosis.
Purpose of the Study:
- To identify and purify components of Borrelia recurrentis that stimulate human monocytes to produce TNF.
- To investigate the role of these components in the pathogenesis of borreliosis, including Lyme disease.
Main Methods:
- Quantitative purification of Borrelia recurrentis components.
- Assaying the ability of purified components to stimulate TNF production in human monocytes.
- Serological analysis for antibodies against identified components in patients.
Main Results:
- A variable lipoprotein, homologous to the variable major protein (VMP) of Borrelia hermsii, was identified as the predominant TNF-inducing factor.
- Antibodies to different VMP forms were detected in patients with louse-borne relapsing fever.
- Variations in the TNF-inducing capacity of different VMPs were observed, potentially explaining differences in clinical disease severity.
Conclusions:
- Variable lipoproteins of Borrelia recurrentis are key inducers of TNF, driving Jarisch-Herxheimer reactions.
- The findings provide insights into the variable clinical manifestations of borreliosis.
- This research has implications for understanding the pathogenesis of Lyme disease and other human borrelioses.
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