FOR 729: Anti-infective Effector Programmes: Signals and Mediators
Final Report Abstract
The immune system is steadily challenged by a wide variety of pathogens. Its task is the elimination or control of pathogens by activation and execution of adequate effector programs. Invading pathogens are sensed and identified by specific immune receptors as a prerequisite for the initiation of antiinfectious immune effector programs. Immediately after pathogen encounter, immune responses are activated and the appropriate humoral and cellular components of the immune system which are essential for the generation of innate and adaptive effector programs are recruited. During the co-evolution of hosts and pathogens, especially intracellularly replicating pathogens have evolved strategies which specifically circumvent or blunt the activation or execution of antiinfectious effector programs. While the knowledge on the mechanisms of immune recognition of pathogens on the molecular level has been pivotally advanced during the recent years [pathogen associated molecular patterns (PAMPs) / activating immunoreceptors (TLRs/NLRs)], the understanding of the molecular immunological mechanisms responsible for the eradication or control of pathogens as well as of the modulation and inactivation of immune effector mechanism through interception strategies of pathogens has not been advanced adequately so far. Therefore, the strategic goals of the Research Unit have been put forward to encompass a research program focusing on the identification of immune effector mechanisms and their molecular components, understanding of the activation and regulation of immune effector mechanisms, and the investigation of the interference of pathogens with immunological effector programs. Thus, it was of utmost importance to unravel the endogenous principles of antimicrobial immune defenses. The conceptual approach of the research unit focuses on the activation of immunological effector programs which are directed against pathogens that have developed virulence strategies enabling intracellular replication with or without latency inside the host (Chlamydia pneumoniae, Listeria monocytogenes, Hepatitis C virus, cytomegalovirus, Toxoplasma gondii). Using this set of representative pathogens prototypical interference mechanisms have been unraveled which lead to the inactivation of essential effector molecules. Another essential component of the research program encompasses the systematic identification and characterization of known and novel immune effector programs (interferon γ regulated guanylate binding proteins of the 65 kDa family, HIF1α-controlled effector programs, indoleamine 2,3-dioxygenase). In parallel, the research unit concentrated on the improvement of knowledge on afferent processes during activation and recruitment of immune effector cell populations via chemokines and the visualization of immune responsive cells. Results obtained within the Research Unit advanced our knowledge on the targeting of host defense molecules and the counteracting virulence factors of pathogens. The common scientific research aims of all projects of the Research Unit was the unraveling of the complex host-pathogen relationship in the context of cellular microbiology and immunology in model systems and the exploration of novel effector mechanisms that mediate the inactivation of pathogens. The knowledge base for these research goals could be successfully advanced within the funding period of the Research Unit by a highly fruitful interaction of the researchers involved. The gained knowledge in basic and translational research was successfully disseminated during the international conferences of Research Unit. The projects have provided seminal advances in the understanding of host immune effector mechanisms and interference programs of pathogens.
