The biological role of interferon-y induced 65 kDa GBPs as effector molecules in host defense

This project focuses on the characterization of novel antimicrobial effector molecules that are regulated by IFNγ. These molecules, called 65 kDa guanylate-binding proteins (GBPs) are abundantly induced by IFNγ, but their functions are still enigmatic. In the scientific program of this Research Unit project 6 novel members of the mGBP family (mGBP 6, -7, -8, -9, -10, and -11) could be identified. It was established that all 11 members of the mGBP family are inducible by IFNγ and are rapidly induced in mice after infection with L. monocytogenes and T. gondii. Remarkably, several mGBPs (mGBP 1, -2, -3, -6, -7, and -9) show a subcellular redistribution and direct colocalization with the parasitophorous vacuole of  T. gondii parasites. During the first funding period, gene-deficient mice for several mGBPs (mGBP1, -2, -3, and 5) were successfully generated. The aim of the proposed 2nd project period is the characterization of the molecular effects of the mGBP proteins on diverse pathogens and the in vivo role of distinct GBP molecules in the defense against bacterial, viral, and parasitic infections.

Prof. Dr. med. Klaus Pfeffer
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University of Düsseldorf

TP6 in period 2007-2009

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