Institute of Virology

On a global scale one third of the human population is infected with T. gondii although local rates vary significantly. Three genetically almost identical lineages (clonal lineages) predominate in Europe and North America. All clonal lineages infect a variety of hosts, including humans.

Resistance against infection by T. gondii in mice is largely dependent on a family of IFNγ-inducible proteins, the Immunity-related GTPases (IRG proteins). IRG proteins accumulate in high densities at the membrane surrounding intracellular T. gondii called the parasitophorous vacuolar membrane (PVM). Loading is an absolute prerequisite for membrane disintegration and subsequent death of the parasite. T. gondii has evolved distinct mechanisms to overcome this cell-autonomous immune mechanism. Polymorphic virulence effectors of the parasite are secreted upon and after host cell invasion from a set of different secretory organelles and are partially redirected to the PVM. IRG protein inactivation at the PVM is achieved by highly specific multicomponent complexes composed of diverse effector proteins. We want to identify yet unknown molecular effector mechanisms of T. gondii for the complex attack on the IRG resistance system in laborytory strains of mice.

Another part of our research is dedicated to virulence of T. gondii in non-laboratory strains of mice.

Polymorphic T. gondii effector proteins are confronted with polymorphic IRG proteins in certain mice. These polymorphic IRG proteins mice counteract parasite effector proteins and therefore suppress virulence of the pathogen possibly following a “gene for gene” pattern.

We started to describe the molecular basis for resistance of wild-derived mice against virulent T. gondii strains.

These mice are however not resistant to all virulent T. gondii strains. Confrontation with polymorphic IRG proteins in the wild results in evolution of certain pathogen variants that are able to escape this immune response. This could be shown for certain „atypical“ T. gondii strains from South America.

We want to reveal the constituents that allow „atypical“ T. gondii strains to escape the resistance mechanism of wild-derived mice.