Conflict of InterestsThe authors CYC202 declare that they have no conflict of interests.AcknowledgmentsThe authors are thankful to Dr. Kalyan Raman and Dr. Hamid Iqbal Tak for their valuable suggestions and proof reading. Shohreh Azizi thanks the North West University, South Africa, for the award of a postdoctoral fellowship in 2013.
Toxoplasma gondii is an obligate intracellular parasite, which is able to infect almost all warm-blooded animals. The virulence of T. gondii is strain-dependent. Based on genetic polymorphisms analysis of T. gondii isolated from infected patients, the virulence of T. gondii was found to be clustered in three classes [1]. This virulence classification was confirmed in mouse infection experiments.

While infection with only one parasite of a class I strain is sufficient to kill a mouse, up to 105 parasites are required of a type II or III strain [2]. In an experimental model of a protozoan brain infection, parasite replication is eventually restricted by the immune system. The tachyzoites in the acute stage convert under the immune pressure to bradyzoites initiating the chronic stage of infection [3]. In this silent phase the formed cysts are no longer detected by the immune systems and persist in the CNS��predominantly in astrocytes [4], in skeletal muscles, and cardiac tissue [5]. Nevertheless, occasionally bradyzoite cysts will rupture inducing a rapid recruitment of inflammatory cells [6]. Infection experiments with mice deficient for various genes proved the importance of interferon (IFN)��; IFN��-deficient mice die in the acute phase during the first week of infection [7].

The importance of nonphagocytic cells in the defence against T. gondii was clearly demonstrated in bone marrow chimera experiments with IFN��-deficient mice. Thus, for control of T. gondii not only the cells of the hematopoietic system which are important but also the cells of nonhematopoietic origin [8]. IFN�� induces a whole set of defence mechanisms in classical phagocytotic cells like macrophages. However, astrocytes��the main cell population infected in the Drug_discovery brain��are not equipped with most of the defence mechanisms like NO production and indoleamine dioxygenase (IDO) mediated tryptophan degradation [9]. Therefore, up to now, the defence system of cells of nonhematopoietic origin like astrocytes has been unknown. Recently, a new group of IFN�� induced p47kDa immunity-related GTPases (IRGs) has been shown to have a major impact on the ability of the host to overcome T. gondii infection. Mice deficient for the p47 GTPase Irgm3 (formerly referred to as IGTP) or Irgm1 (LRG-47) succumb within the acute phase of infection [10, 11]. Also for Irga6 (IIGP, IIGP1) a reduced resistance against Toxoplasma was demonstrated [12].