Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease

Am J Pathol. 2011 Jun;178(6):2726-39. doi: 10.1016/j.ajpath.2011.02.018.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Borrelia burgdorferi / drug effects
  • Borrelia burgdorferi / genetics*
  • Borrelia burgdorferi / isolation & purification
  • Chemokines / blood
  • Chemokines / metabolism
  • Drug Resistance, Bacterial / drug effects
  • Erythema / blood
  • Erythema / complications
  • Erythema / microbiology
  • Erythema / pathology
  • Humans
  • Inflammation / blood
  • Inflammation / complications*
  • Inflammation / microbiology*
  • Inflammation / pathology
  • Joints / drug effects
  • Joints / pathology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / microbiology
  • Lyme Disease / blood
  • Lyme Disease / complications*
  • Lyme Disease / drug therapy
  • Lyme Disease / microbiology*
  • Lyme Disease / pathology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Synovial Fluid / drug effects
  • Synovial Fluid / metabolism

Substances

  • Anti-Bacterial Agents
  • Chemokines