Matrix metalloproteinase 9 plays a key role in lyme arthritis but not in dissemination of Borrelia burgdorferi.
Borrelia burgdorferi, the causative agent of Lyme arthritis, does not produce any exported proteases capable of degrading extracellular matrix despite the fact that it is able to disseminate from a skin insertion site to infect multiple organs. Prior studies have shown that B. burgdorferi induces the host protease, matrix metalloproteinase 9 (MMP-9), and suggested that the induction of MMP-9 may allow the organism to disseminate and produce local tissue destruction. We examined the role of MMP-9 in dissemination of B. burgdorferi and pathogenesis of Lyme arthritis. In a MMP-9(-/-) mouse model, MMP-9 was not required for the dissemination of the spirochete to distant sites. However, MMP-9(-/-) exhibited significantly decreased arthritis compared to wild-type mice. The decrease in arthritis was not due to an inability to control infection since the spirochete numbers in the joints were identical. Levels of inflammatory chemokines and cytokines were also similar in MMP-9(-/-) and wild-type mice. We examined whether decreased inflammation in MMP-9(-/-) mice may be the result of decreased production of neoattractants by MMP-9-dependent cleavage of collagen. MMP-9 cleavage of type I collagen results in increased monocyte chemoattraction. MMP-9 plays an important role in regulating inflammation in Lyme arthritis, potentially through the cleavage of type I collagen.
Department of Medicine, Division of Geographic Medicine and Infectious Disease, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Andrew J
AJ
Heilpern
Warren
W
Wertheim
Jia
J
He
George
G
Perides
Roderick T
RT
Bronson
Linden T
LT
Hu
D000818:Animals; D025065:Borrelia burgdorferi / Q000472:pathogenicity*; D024042:Collagen Type I / Q000378:metabolism*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D007596:Joints / Q000382:microbiology / Q000473:pathology; D008193:Lyme Disease / Q000382:microbiology* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014774:Virulence
D024042:Collagen Type I; D016207:Cytokines; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse