title: Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved.
abstract: Lipoteichoic acid (LTA) derived from Streptococcus pneumoniae, purified employing a chloroform/methanol protocol, and from Staphylococcus aureus, prepared by the recently described butanol extraction procedure, was investigated regarding its interaction with lipopolysaccharide (LPS)-binding protein (LBP), CD14, Toll-like receptors (TLRs)-2 and -4, and MD-2. LTA from both organisms induced cytokine synthesis in human mononuclear phagocytes. Activation was LBP- and CD14-dependent, and formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis. Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2. Additional transfection with MD-2 did not affect stimulation of these cells by LTA. Our data suggest that innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by the clinically most important Gram-positive pathogens. However, the involvement of TLR-4 and MD-2 in this process was ruled out.
authors.affiliation: Institut für Mikrobiologie und Hygiene, Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität zu Berlin, Dorotheenstrasse 96, D-10117 Berlin, Germany.
authors.forename: Nicolas W J
authors.initials: NW
authors.lastname: Schröder
authors.forename: Siegfried
authors.initials: S
authors.lastname: Morath
authors.forename: Christian
authors.initials: C
authors.lastname: Alexander
authors.forename: Lutz
authors.initials: L
authors.lastname: Hamann
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.forename: Joerg R
authors.initials: JR
authors.lastname: Weber
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D016466:CHO Cells; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000032:analysis / Q000633:toxicity*; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000032:analysis / Q000633:toxicity*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000954:Antigens, Surface; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C495377:LY96 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C009900:lipoteichoic acid