IIGP1 is a member of the p47 GTPase family of IFNγ-induced proteins, which are among the most potent presently known mediators of cell-autonomous resistance against intracellular bacterial and protozoan pathogens in the mouse. From all studied members of this family IIGP1 is the best characterized with respect to biochemical characteristics and enzymatic activity in vitro, as well as membrane binding properties and dynamic behavior in cells. The role of the protein in intracellular defense was however, unknown and this study was set as an initial attempt to reveal it. This thesis describes the generation of an IIGP1 deficient mouse and analysis of the susceptibility of this animal to pathogens from protozoan and bacterial origin, which employ diverse strategies for host cell invasion and intracellular survival and replication. Despite having intact adaptive immune system, the IIGP1 deficient mice showed higher incidence of development of cerebral malaria after infection with Plasmodium berghei sporozoites. In addition, IIGP1 deficient astrocytes exhibited a partial loss of IFNγ-induced inhibition of Toxoplasma gondii growth. IIGP1 deficient animals were not susceptible to infection with Leishmania major, Listeria monocytogenes, Chlamydia trachomatis and Anaplasma phagocytophilum. From the analysis of the obtained data in the context of the intracellular lifestyle of the pathogens involved in this study, we concluded that IIGP1 seems to be specifically involved in defense against protozoan parasites, which like Pl. berghei and T. gondii reside in non-fusigenic parasitophorous vacuoles after entering cells. The mechanisms of IIGP1-dependent protection of cells against these pathogens remain to be studied
