Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.
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.
Lien
E
E
Maxwell Finland Laboratory for Infectious Diseases, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Sellati
T J
TJ
Yoshimura
A
A
Flo
T H
TH
Rawadi
G
G
Finberg
R W
RW
Carroll
J D
JD
Espevik
T
T
Ingalls
R R
RR
Radolf
J D
JD
Golenbock
D T
DT
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D015748:Borrelia burgdorferi Group / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D029721:Drosophila Proteins; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009162:Mycobacterium avium / Q000378:metabolism; D016858:Mycoplasma fermentans / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014210:Treponema pallidum / Q000378:metabolism
D001426:Bacterial Proteins; D029721:Drosophila Proteins; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors