Resistance to Lyme disease in decorin-deficient mice

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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 Borrelia-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 Borrelia-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

Eric L. Brown, R. Mark Wooten, Barbara J.B. Johnson, Renato V. Iozzo, Amanda Smith, Marc C. Dolan, Betty P. Guo, Janis J. Weis, Magnus Höök