Regulation of function of innate immune cells through direct and indirect TLR-dependent signals

• Antragsteller: Professor Dr. Klaus Michael Heeg
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2002 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5357562

Microbial patterns are recognized by innate immune cells dependent of Toll-like receptors (TLR). TLR-dependent inducers include constitutive bacterial components like lipopolysaccaride (LPS), lipoteichoic acid (LTA), lipoproteins and immuno-stimulatory bacterial DNA (CpG-DNA). Initially TLR-dependent signals induce activation and induction of effector cell functions. However, following initial activation subsequent feed-back regulatory circuits control the reactivity of macrophages and thus critically influence the fate of an infection. We have shown previously that immuno-stimulatory CpG-DNA induces a negative regulative system which includes proteins of the family of suppressors of cytokine signaling (SOCS). SOCS proteins interfere with intracellular cytokine signaling cascades and thus inhibit further activation and induction of effector cell function. Since these effects are critically in combatting infections we propose here to analyze the signal requirements as well as mechanisms (MyD88-dependency) for induction of these regulatory circuits in macrophages and dendritic cells in vitro and in vivo. In a second line the functional consequences of SOCS expression will be determined in vitro by transfection experiments as well as in vivo after induction of SOCS-proteins by defined TLR-dependent stimuli. These experiments will contribute to our knowledge of the activation and signal pathways of the innate immune system induced by TLR-dependent microbial patterns. Since macrophages and dendritic cell bridge innate and adaptive immune system these investigations will also be important for the subsequent activation of the adaptive immune response.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1110: Angeborene Immunität
• Beteiligte Person: Professor Dr. Alexander Dalpke