FOR 729:  Anti-infective Effector Programmes: Signals and Mediators

• Subject Area: Medicine
• Term: from 2007 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 21644054

The physiological task of the immune system is the eradication of pathogens through the activation and execution of adequate immunological effector programmes. As a prerequisite of the execution of anti-infective effector programmes the invading pathogens (bacteria, viruses, fungi, protozoa, helminthes) must be sensed and identified. Immediately afterwards, recruitment of the adequate humoral and cellular components of the immune system takes place, which are essential for the initiation of the effector programmes that mediate a protective immune response. Through coevolution especially intracellularly replicating pathogens have developed strategies that circumvent or block the execution of immune effector programmes. While the gain of knowledge of mechanisms for the recognition of pathogens have made great progress during the last years (pathogen associated molecular patterns/toll like receptors), advances in the understanding of the molecular mechanisms responsible for the eradication of pathogens as well as the modulation and inactivation of these mechanisms through pathogens have been rather limited.
The aims of the Research Unit encompass the identification of immunological effector mechanism and their components on a molecular level, the understanding of the activation and regulation of effector mechanism and the investigation of interference strategies of pathogens with immunological effector programmes. These challenges are of great importance since many pathogens have developed resistance against the standard anti-infective drugs in the meantime. Therefore, the endogenous principles of the immune defense have to be urgently elucidated for advanced anti-infective therapies.
The conceptual approach of this Research Unit will focus on the immunological effector programmes that are directed against pathogens that rely on virulence factors that enable intracellular replication with or without latency in the host (Chlamydia pneumoniae, Listeria monocytogenes, hepatitis C virus, cytomegalovirus, Toxoplasma gondii). The mutual goal of all projects of the Research Unit is the unravelling of the complex host pathogen interactions of infectious diseases and the exploration of novel mechanisms that are required for the eradication of pathogens.

• DFG Programme: Research Units

Projects

• Antimicrobial effects mediated by the regulation of the local tryptophan concentration: diverse effects mediated by different tryptophan degrading enzymes in mice and men (Applicant Däubener, Walter )
• Central tasks of the Research Unit 729 (Applicant Pfeffer, Klaus )
• Control of CD8+ T cells through interference of Cytomegalovirus with the "peptide loading complex" (PLC) (Applicant Hengel, Hartmut )
• CXCL14/BRAK: Organization of immune defense at barrier organs (Applicant Homey, Bernhard )
• Interference of HCV with anti-infectious and inflammatory effector systems of the host (Applicant Bode, Johannes Georg )
• Mechanismen der Zell- und Isoformspezifität Gi-Protein-abhängiger Signalwege in Entzündungszellen (Applicant Nürnberg, Bernd )
• Metabolic regulation of inflammatory processes: HIF-1alpha and IDO as anti-infectious effector molecules in professional phagocytes (Applicant Förster, Irmgard )
• The biological role of interferon y induced 65 kDa GBPs as effector molecules in host defense (Applicant Pfeffer, Klaus )
• The role of the Chlamydia pneumoniae protein Pmp21 during infection (Applicant Hegemann, Johannes H. )
• Visualization of IL-22 expressing cells during anti-infectious immune responses (Applicant Scheu, Stefanie )

• Spokesperson: Professor Dr. Klaus Pfeffer