Evidence is emerging for differential pathogenicity among Borrelia burgdorferi genotypes in the United States. By using two linked genotyping systems, ribosomal RNA intergenic spacer type (RST) and outer surface protein C (OspC), we studied the inflammatory potential of B. burgdorferi genotypes in cells and patients with erythema migrans or Lyme arthritis. When macrophages were stimulated with 10 isolates of each RST1, RST2, or RST3 strain, RST1 (OspC type A)-stimulated cells expressed significantly higher levels of IL-6, IL-8, chemokine ligand (CCL) 3, CCL4, tumor necrosis factor, and IL-1β, factors associated with innate immune responses. In peripheral blood mononuclear cells, RST1 strains again stimulated significantly higher levels of these mediators. Moreover, compared with RST2, RST1 isolates induced significantly more interferon (IFN)-α, IFN-γ, and CXCL10, which are needed for adaptive immune responses; however, OspC type I (RST3) approached RST1 (OspC type A) in stimulating these adaptive immune mediators. Similarly, serum samples from patients with erythema migrans who were infected with the RST1 genotype had significantly higher levels of almost all of these mediators, including exceptionally high levels of IFN-γ-inducible chemokines, CCL2, CXCL9, and CXCL10; and this pronounced inflammatory response was associated with more symptomatic infection. Differences among genotypes were not as great in patients with Lyme arthritis, but those infected with RST1 strains more often had antibiotic-refractory arthritis. Thus, the B. burgdorferi RST1 (OspC type A) genotype, followed by the RST3 (OspC type I) genotype, causes greater inflammation and more severe disease, establishing a link between spirochetal virulence and host inflammation.
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http://dx.doi.org/10.1016/j.ajpath.2011.02.018 | DOI Listing |
Ticks Tick Borne Dis
November 2024
Division of Infectious Diseases, Wadsworth Center, NYSDOH, Albany, NY, USA; Department of Biomedical Sciences, SUNY Albany, Albany, NY, USA; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. Electronic address:
Tolerance and resistance are two host eco-immunological strategies in response to microparasite invasion. In the strategy of "resistance", host responses are induced to decrease microparasite replication while the "tolerance" strategy allows hosts coexistence with microparasites by minimizing responses to avoid immune-mediated damage. The causative agent of Lyme disease is a group of genotypically diverse bacterial species, Borrelia burgdorferi sensu lato (Bb), which is transmitted by Ixodes ticks and persists in different reservoir animals.
View Article and Find Full Text PDFInfect Immun
November 2024
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Lyme disease, caused by and related species is a growing health threat to companion animals across North America and Europe. Vaccination is an important preventive tool used widely in dogs living in, or near, endemic regions. In this report, we assessed anti-outer surface protein (Osp) A and anti-OspC antibody responses in -infected and -naïve mice (C3H/HeN) after immunization with a murine-optimized single dose of the Lyme disease subunit vaccine, Vanguard crLyme.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2024
Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada and World Health Organization Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, Canada.
The rising prevalence of Lyme disease (LD) in North America and Europe has emerged as a pressing public health concern. Despite the availability of veterinary LD vaccines, no vaccine is currently available for human use. Outer surface protein C (OspC) found on the outer membrane of the causative agent, , has been identified as a promising target for LD vaccine development due to its sustained expression during mammalian infection.
View Article and Find Full Text PDFInfect Immun
June 2024
Department of Molecular Medicine, University of South Florida, Tampa, Florida, USA.
of , the Lyme disease pathogen, encodes a hypothetical protein of unknown function. In this study, we showed that BB0616 was not surface-exposed or associated with the membrane through localization analyses using proteinase K digestion and cell partitioning assays. The expression of was influenced by a reduced pH but not by growth phases, elevated temperatures, or carbon sources during cultivation.
View Article and Find Full Text PDFmSystems
January 2024
Department of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
, the pathogen of Lyme disease, differentially produces many outer surface proteins (Osp), some of which represent the most abundant membrane proteins, such as OspA, OspB, and OspC. In cultured bacteria, these proteins can account for a substantial fraction of the total cellular or membrane proteins, posing challenges to the identification and analysis of non-abundant proteins, which could serve as novel pathogen detection markers or as vaccine candidates. Herein, we introduced serial mutations to remove these abundant Osps and generated a mutant deficient in OspA, OspB, and OspC in an infectious 297-isolate background, designated as mutant.
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