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J Biol Chem, Vol. 274, Issue 47, 33419-33425, November 19, 1999
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From the Toll-like receptors (TLRs) 2 and 4 are signal
transducers for lipopolysaccharide, the major proinflammatory
constituent in the outer membrane of Gram-negative bacteria. We
observed that membrane lipoproteins/lipopeptides from Borrelia
burgdorferi, Treponema pallidum, and Mycoplasma
fermentans activated cells heterologously expressing TLR2 but not
those expressing TLR1 or TLR4. These TLR2-expressing cells were also
stimulated by living motile B. burgdorferi, suggesting that
TLR2 recognition of lipoproteins is relevant to natural
Borrelia infection. Importantly, a TLR2 antibody inhibited
bacterial lipoprotein/lipopeptide-induced tumor necrosis factor release
from human peripheral blood mononuclear cells, and TLR2-null Chinese
hamster macrophages were insensitive to lipoprotein/lipopeptide
challenge. The data suggest a role for the native protein in cellular
activation by these ligands. In addition, TLR2-dependent
responses were seen using whole Mycobacterium avium and
Staphylococcus aureus, demonstrating that this receptor can
function as a signal transducer for a wide spectrum of bacterial products. We conclude that diverse pathogens activate cells through TLR2 and propose that this molecule is a central pattern recognition receptor in host immune responses to microbial invasion.
Maxwell Finland Laboratory for Infectious
Diseases, Boston University Medical Center,
Boston, Massachusetts 02118, the § Institute of Cancer
Research and Molecular Biology, Norwegian University of Science and
Technology, 7489 Trondheim, Norway, the ¶ Center for Microbial
Pathogenesis, University of Connecticut Health Center,
Farmington, Connecticut 06030, the Département de
Bacteriologie, Institut Pasteur, 75724 Paris Cedex 15, France, the
Department of Medicine, Boston University
School of Medicine, Boston Veterans Affairs Medical Center,
Boston, Massachusetts 02130, and the ** Laboratory of Infectious
Diseases, Dana-Farber Cancer Institute,
Boston, Massachusetts 02115
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