title: Cytokine induction by Gram-positive bacteria.
abstract: Despite similar clinical relevance of Gram-positive and Gram-negative infections, immune activation by Gram-positive bacteria is by far less well understood than immune activation by Gram-negative bacteria. Our group has made available highly purified lipoteichoic acids (LTA) as a key Gram-positive immunostimulatory component. We have characterized the reasons for lower potency of LTA compared to Gram-negative lipopolysaccharide (LPS), identifying lack of IL-12/IFNgamma induction as a general characteristic of TLR2 agonists, and need for presentation of LTA on surfaces for enhanced immunostimulatory potency, as major aspects. Aspects of chemokine induction, where LTA is more potent than LPS, have been addressed. Furthermore, novel complement and plant defence activation, as well as CD36 as a new LTA receptor, were identified. The bacterial costimuli and modulators of LTA inducible responses are being investigated: LTA isolated from so far 16 bacterial species, although different in structure, behave remarkably similar while whole live and killed bacteria differ with regard to the pattern of induced responses. The purification and characterization of the respective components of the bacterial cell wall has begun.
authors.affiliation: Biochemical Pharmacology, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Draing
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sigel
authors.forename: Susanne
authors.initials: S
authors.lastname: Deininger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Traub
authors.forename: Rebekka
authors.initials: R
authors.lastname: Munke
authors.forename: Christoph
authors.initials: C
authors.lastname: Mayer
authors.forename: Lars
authors.initials: L
authors.lastname: Hareng
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
authors.forename: Corinna
authors.initials: C
authors.lastname: Hermann
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism; D018955:CD36 Antigens / Q000096:biosynthesis; D002473:Cell Wall / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D013682:Teichoic Acids / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D018664:Interleukin-12; C009900:lipoteichoic acid; D007371:Interferon-gamma