Cytokine induction by Gram-positive bacteria

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Despite similar clinical relevance of Gram-positive and Gram-negative infection, immune activation by Gram-positive bacteria is by far less well understood than immune activation by Gram-negative bacteria. Our group has made available highlypurified lipoteichoic acids (LTA) as a key Gram-positive immune stimulatory component. The first phase of the project characterised the reasons for lower potency of LTA compared to Gram-negative lipopolysaccharide (LPS) identifying lack of IL-12/IFNy induction as a general characteristic of TLR2 agonists and need for presentation of LTA on surfaces for enhanced immunostimulatory potency as major aspects. The second phase addressed aspects of chemokine induction, where LTA is more potent than LPS, and further characterized the phenomenon of LTA presentation. Furthermore, within collaborations of SPP 1110, novel complement and plant defence activation as well as CD36 as a new LTA receptor were identified. The final project phase shall address the bacterial costimuli and modulators of LTA inducible responses: 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 respective components of the bacterial cell wall shall be purified and characterised.