Evidence is emerging for differential pathogenicity among Borrelia burgdorferigenotypes 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 incells and patients with erythema migrans or Lyme arthritis. When macrophageswere 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-1beta, 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 inducedsignificantly more interferon (IFN)-alpha, IFN-gamma, and CXCL10, whichare 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-gamma-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.
F.02 Acquisition of new scientific knowledge
COBISS.SI-ID: 28725721The chapter on European Lyme borreliosis published in an American monography on Lyme disease.
C.01 Editorial board of a foreign/international collection of papers/book
COBISS.SI-ID: 28906969Symposium devoted to antimicrobial resistance with published presentations.
C.02 Editorial board of a national monograph
COBISS.SI-ID: 255411968