title: Cytokine-inducing lipoteichoic acids of the allergy-protective bacterium Lactococcus lactis G121 do not activate via Toll-like receptor 2.
abstract: It was established in a mouse model that the cowshed Gram-positive bacterium Lactococcus lactis G121 modulates the immune system resulting in allergy protection. However, the molecules and mechanisms involved in this process have not been elucidated yet. Lipoteichoic acids (LTAs) represent one major cell envelope component of Gram-positive bacteria that is considered a pathogen-associated molecular pattern. In the investigations presented here, the isolation as well as the structural and functional analyses of the LTA of L. lactis G121 were performed. Extraction with butan-1-ol and purification by hydrophobic interaction chromatography yielded pure LTA. Structural investigations included chemical analytical methods, nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization Fourier-transformed ion cyclotron mass spectrometry. LTA comprised a heterogeneous mixture of molecules composed of a 1,3-linked poly(glycerol phosphate) backbone which was randomly substituted at C-2 by D-alanine and α-D-galactopyranose. The lipid anchor constituents were kojibiose linked to a heterogeneous diglyceride comprising in total six different fatty acid compositions. This LTA preparation possesses Toll-like receptor 2- (TLR2) and TLR4-independent cytokine-inducing activities in human mononuclear cells.
authors.affiliation: Division of Structural Biochemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1- 40, D-23845 Borstel, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Fischer
authors.forename: Karina
authors.initials: K
authors.lastname: Stein
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Buko
authors.initials: B
authors.lastname: Lindner
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Otto
authors.initials: O
authors.lastname: Holst
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D013294:Lactococcus lactis / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D013682:Teichoic Acids / Q000737:chemistry / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid