Cytokine induction by Gram-positive bacteria.
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.
Draing
Christian
C
Biochemical Pharmacology, University of Konstanz, 78457 Konstanz, Germany.
Sigel
Stefanie
S
Deininger
Susanne
S
Traub
Stephanie
S
Munke
Rebekka
R
Mayer
Christoph
C
Hareng
Lars
L
Hartung
Thomas
T
von Aulock
Sonja
S
Hermann
Corinna
C
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
D018955:CD36 Antigens; D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D018664:Interleukin-12; C009900:lipoteichoic acid; D007371:Interferon-gamma