title: Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.
abstract: 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.
authors.affiliation: Maxwell Finland Laboratory for Infectious Diseases, Boston University Medical Center, Boston, Massachusetts 02118, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lien
authors.forename: T J
authors.initials: TJ
authors.lastname: Sellati
authors.forename: A
authors.initials: A
authors.lastname: Yoshimura
authors.forename: T H
authors.initials: TH
authors.lastname: Flo
authors.forename: G
authors.initials: G
authors.lastname: Rawadi
authors.forename: R W
authors.initials: RW
authors.lastname: Finberg
authors.forename: J D
authors.initials: JD
authors.lastname: Carroll
authors.forename: T
authors.initials: T
authors.lastname: Espevik
authors.forename: R R
authors.initials: RR
authors.lastname: Ingalls
authors.forename: J D
authors.initials: JD
authors.lastname: Radolf
authors.forename: D T
authors.initials: DT
authors.lastname: Golenbock
mesh_terms: 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
chemical_list: 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