SPEAKER Prof. Dr. Klaus PFEFFER Professor Heinrich-Heine-University Düsseldorf, Institute of Medical Microbiology. Director, Institute of Medical Microbiology and Hospital Hygiene. HOST: Department of Infection and Immunity RESPONSIBLE LIH SCIENTIST: Prof Markus Ollert (markus.ollert@lih.lu) www.lih.lu INTERFERON INDUCIBLE GUANYLATE BINDING PROTEINS (GBPS) IN IMMUNE DEFENSE ABSTRACT Host defense against invading pathogens is critically dependent upon interferon induced anti-microbial effector programs. Recently, we have discovered that vast number of interferon induced genes are GTPases belonging to the family of guanylate binding proteins (GBPs). GBPs are essential for immunity against intracellular pathogens, especially for Toxoplasma gondii control. Now the molecular interactions of murine GBPs (mGBP1/2/3/5/6), homo- and hetero-multimerization properties of mGBP2 and its function in parasite killing were investigated by mutational, Multiparameter Fluorescence Image Spectroscopy, and live cell microscopy methodologies. Control of T. gondii replication by mGBP2 requires GTP hydrolysis and isoprenylation thus, enabling reversible oligomerization in vesicle-like structures. mGBP2 undergoes structural transitions between monomeric, dimeric and oligomeric states visualized by quantitative FRET analysis. mGBPs reside in at least two discrete subcellular reservoirs and attack the parasitophorous vacuole membrane (PVM) as orchestrated, supramolecular complexes forming large, densely packed multimers comprising up to several thousand monomers. This dramatic mGBP enrichment results in the loss of PVM integrity, followed by a direct assault of mGBP2 upon the plasma membrane of the parasite. These discoveries provide vital dynamic and molecular perceptions into cell-autonomous immunity. * Opposite Luxembourg Institute of Health, House of BioHealth, 29, rue Henri Koch L-4354 Esch/Alzette Supported by: