Resistance to Lyme disease in decorin-deficient mice.

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.

• Authors: E L Brown, R M Wooten, B J Johnson, R V Iozzo, A Smith, M C Dolan, B P Guo, J J Weis, M Höök
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 107 Issue 7 Pg. 845-52 (Apr 2001) ISSN: 0021-9738 [Print] United States
• PMID: 11285303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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