Resistance to Lyme Disease in Decorin-Deficient Mice

J Clin Invest. 2001 Apr;107(7):845-52. doi: 10.1172/JCI11692.

Abstract

Microbial adhesion to the host tissue represents an early, critical step in the pathogenesis of most infectious diseases. BORRELIA: burgdorferi, the causative agent of Lyme disease (LD), expresses two surface-exposed decorin-binding adhesins, DbpA and DbpB. A decorin-deficient (Dcn(-/-)) mouse was recently developed and found to have a relatively mild phenotype. We have now examined the process of experimental LD in Dcn(-/-) mice using both needle inoculation and tick transmission of spirochetes. When exposed to low doses of the infective agent, Dcn(-/-) mice had fewer Borrelia-positive cultures from most tissues analyzed than did Dcn(+/+) or Dcn(+/-) mice. When the infection dose was increased, similar differences were not observed in most tissues but were seen in bacterial colonization of joints and the extent of Borreila-induced arthritis. Quantitative PCR demonstrated that joints harvested from Dcn(-/-) mice had diminished Borrelia numbers compared with issues harvested from Dcn(+/+) controls. Histological examination also revealed a low incidence and severity of arthritis in Dcn(-/-) mice. Conversely, no differences in the numbers of Borreila-positive skin cultures were observed among the different genotypes regardless of the infection dose. These differences, which were observed regardless of genetic background of the mice (BALB/c or C3H/HeN) or method of infection, demonstrate the importance of decorin in the pathogenesis of LD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Borrelia burgdorferi Group / immunology
  • Borrelia burgdorferi Group / pathogenicity*
  • Decorin
  • Disease Models, Animal
  • Extracellular Matrix Proteins
  • Female
  • Immunity, Innate
  • Ixodes
  • Lyme Disease / immunology
  • Lyme Disease / microbiology
  • Lyme Disease / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Knockout
  • Proteoglycans / genetics
  • Proteoglycans / immunology
  • Proteoglycans / physiology*

Substances

  • Dcn protein, mouse
  • Decorin
  • Extracellular Matrix Proteins
  • Proteoglycans