Resistance to Lyme disease in decorin-deficient mice.

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.

[1]  M. Höök,et al.  MSCRAMM-mediated adherence of microorganisms to host tissues. , 1994, Annual review of microbiology.

[2]  P. François,et al.  Use of adhesion-defective mutants of Staphylococcus aureus to define the role of specific plasma proteins in promoting bacterial adhesion to canine arteriovenous shunts , 1995, Infection and immunity.

[3]  M. Mbow,et al.  Effects of Ixodes scapularis and Borrelia burgdorferi on modulation of the host immune response: induction of a TH2 cytokine response in Lyme disease-susceptible (C3H/HeJ) mice but not in disease-resistant (BALB/c) mice , 1997, Infection and immunity.

[4]  S. Bodary,et al.  Integrins αvβ3 and α5β1 Mediate Attachment of Lyme Disease Spirochetes to Human Cells , 1998, Infection and Immunity.

[5]  J. Piesman Standard system for infecting ticks (Acari: Ixodidae) with the Lyme disease spirochete, Borrelia burgdorferi. , 1993, Journal of medical entomology.

[6]  H. Kresse,et al.  Non-uniform influence of transforming growth factor-beta on the biosynthesis of different forms of small chondroitin sulphate/dermatan sulphate proteoglycan. , 1990, The Biochemical journal.

[7]  E. Ruoslahti,et al.  Transforming growth factor-β1 induces extracellular matrix formation in glomerulonephritis , 1990 .

[8]  J. Leong,et al.  Identification of a candidate glycosaminoglycan‐binding adhesin of the Lyme disease spirochete Borrelia burgdorferi , 2000, Molecular microbiology.

[9]  H. Kresse,et al.  Influence of decorin on fibroblast adhesion to fibronectin. , 1991, European journal of cell biology.

[10]  J. Weis,et al.  Rapid and Sensitive Quantification ofBorrelia burgdorferi-Infected Mouse Tissues by Continuous Fluorescent Monitoring of PCR , 1999, Journal of Clinical Microbiology.

[11]  D. Fish,et al.  Suppression of acute Ixodes scapularis-induced Borrelia burgdorferi infection using tumor necrosis factor-alpha, interleukin-2, and interferon-gamma. , 1996, The Journal of infectious diseases.

[12]  C. Teuscher,et al.  Distinct Characteristics of Resistance toBorrelia burgdorferi-Induced Arthritis in C57BL/6N Mice , 1998, Infection and Immunity.

[13]  S. Bodary,et al.  Characterization of a candidate Borrelia burgdorferiβ3‐chain integrin ligand identified using a phage display library , 1999, Molecular microbiology.

[14]  D. Fish,et al.  Suppression of Acute Ixodes scapularis-Induced Borrelia burgdorferi Infection using Tumor Necrosis Factor-α, Interleukin-2, and Interferon-γ , 1996 .

[15]  T. Schwan,et al.  Variable small protein (Vsp)‐dependent and Vsp‐independent pathways for glycosaminoglycan recognition by relapsing fever spirochaetes , 2000, Molecular microbiology.

[16]  J. Benach,et al.  Interaction between Borrelia burgdorferi and endothelium in vitro. , 1990, The Journal of clinical investigation.

[17]  Ennis,et al.  Vaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant , 2000 .

[18]  Charles R. Brown,et al.  Genetic Control of Experimental Lyme Arthritis in the Absence of Specific Immunity , 1999, Infection and Immunity.

[19]  H. Kresse,et al.  Interactions between thrombospondin and the small proteoglycan decorin: interference with cell attachment. , 1992, European journal of cell biology.

[20]  R. D. Isaacs Borrelia burgdorferi bind to epithelial cell proteoglycans. , 1994, The Journal of clinical investigation.

[21]  J. Coburn,et al.  Integrin alpha IIb beta 3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Halperin,et al.  Failure of tetracycline therapy in early Lyme disease. , 1987, Arthritis and rheumatism.

[23]  F. Reinholt,et al.  Fibromodulin-null Mice Have Abnormal Collagen Fibrils, Tissue Organization, and Altered Lumican Deposition in Tendon* , 1999, The Journal of Biological Chemistry.

[24]  B. P. Guo,et al.  Decorin‐binding adhesins from Borrelia burgdorferi , 1998, Molecular microbiology.

[25]  A. Barbour Isolation and cultivation of Lyme disease spirochetes. , 1984, The Yale journal of biology and medicine.

[26]  B. P. Guo,et al.  Adherence of Borrelia burgdorferi to the proteoglycan decorin , 1995, Infection and immunity.

[27]  A. Stere SUCCESSFUL PARENTERAL PENICILLIN THERAPY OF ESTABLISHED LYME ARTHRITIS , 1985 .

[28]  R. Iozzo,et al.  The family of the small leucine-rich proteoglycans: key regulators of matrix assembly and cellular growth. , 1997, Critical reviews in biochemistry and molecular biology.

[29]  G. Boivin,et al.  Inhibition of collagen-induced arthritis in mice by viral IL-10 gene transfer. , 1998, Journal of immunology.

[30]  S. Barthold,et al.  Lyme borreliosis in selected strains and ages of laboratory mice. , 1990, The Journal of infectious diseases.

[31]  S. Bodary,et al.  Integrins alpha(v)beta3 and alpha5beta1 mediate attachment of lyme disease spirochetes to human cells. , 1998, Infection and immunity.

[32]  A. Tarkowski,et al.  The Staphylococcus aureus collagen adhesin is a virulence determinant in experimental septic arthritis , 1994, Infection and immunity.

[33]  J. Volanakis,et al.  The proteoglycan decorin binds C1q and inhibits the activity of the C1 complex. , 1992, Journal of immunology.

[34]  S. Norris,et al.  Correlation between plasmid content and infectivity in Borrelia burgdorferi. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  S. Barthold,et al.  Diverse Lyme disease spirochetes bind integrin alpha IIb beta 3 on human platelets , 1994, Infection and immunity.

[36]  C. Schmid,et al.  Treatment of Lyme arthritis. , 1994, Arthritis and rheumatism.

[37]  A. Steere Lyme disease. , 1989, The New England journal of medicine.

[38]  M. Klempner,et al.  Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. , 1993, The Journal of infectious diseases.

[39]  S. Barthold,et al.  Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. , 1992, The American journal of tropical medicine and hygiene.

[40]  Renato V. Iozzo,et al.  Targeted Disruption of Decorin Leads to Abnormal Collagen Fibril Morphology and Skin Fragility , 1997, Journal of Cell Biology.

[41]  J. Benach,et al.  Lyme borreliosis: host responses to Borrelia burgdorferi. , 1991, Microbiological reviews.

[42]  Barbara J. B. Johnson,et al.  Identification of a 47 kDa fibronectin‐binding protein expressed by Borrelia burgdorferi isolate B31 , 1998, Molecular microbiology.

[43]  C. Schmid,et al.  Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. , 1998, The New England journal of medicine.

[44]  M. Cinco,et al.  Integrin CR3 mediates the binding of nonspecifically opsonized Borrelia burgdorferi to human phagocytes and mammalian cells , 1997, Infection and immunity.

[45]  R. M. Wooten,et al.  Dual Role of Interleukin-10 in Murine Lyme Disease: Regulation of Arthritis Severity and Host Defense , 1999, Infection and Immunity.

[46]  A. Steere Medical progress. Lyme disease , 1989 .

[47]  A. Giordano,et al.  Decorin-induced Growth Suppression Is Associated with Up-regulation of p21, an Inhibitor of Cyclin-dependent Kinases* , 1996, The Journal of Biological Chemistry.

[48]  R. Iozzo Matrix proteoglycans: from molecular design to cellular function. , 1998, Annual review of biochemistry.

[49]  C. Peschle,et al.  The Retinoblastoma Family Member p107 Binds to B-MYB and Suppresses Its Autoregulatory Activity* , 1996, The Journal of Biological Chemistry.

[50]  S. Norris,et al.  Specific Th1 cell lines that confer protective immunity against experimental Borrelia burgdorferi infection in mice , 1998, Journal of leukocyte biology.