Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2.
The agent of Lyme disease, Borrelia burgdorferi, produces membrane lipoproteins possessing potent inflammatory properties linked to disease pathology. The recent association of toll-like receptors (TLR) 2 and 4 with LPS responses prompted the examination of TLR involvement in lipoprotein signaling. The ability of human cell lines to respond to lipoproteins was correlated with the expression of TLR2. Transfection of TLR2 into cell lines conferred responsiveness to lipoproteins, lipopeptides, and sonicated B. burgdorferi, as measured by nuclear translocation of NF-kappaB and cytokine production. The physiological importance of this interaction was demonstrated by the 10-fold greater sensitivity of TLR2-transfected cells to lipoproteins than LPS. Futhermore, TLR2-dependent signaling by lipoproteins was facilitated by CD14. These data indicate that TLR2 facilitates the inflammatory events associated with Lyme arthritis. In addition, the widespread expression of lipoproteins by other bacterial species suggests that this interaction may have broad implications in microbial inflammation and pathogenesis.
Hirschfeld
M
M
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Kirschning
C J
CJ
Schwandner
R
R
Wesche
H
H
Weis
J H
JH
Wooten
R M
RM
Weis
J J
JJ
D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001428:Bacterial Vaccines; D001692:Biological Transport / Q000276:immunology; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D029721:Drosophila Proteins; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D029721:Drosophila Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C072045:OspA protein; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors