ABSTRACT
M acrophages and other host cells possess an array of effector mechanisms that restrict intracellular replication of Toxoplasma gondii in a cell autonomous manner. These effectors are diverse and include proteins such as phagocyte oxidase that catalyze the production of substances toxic to T. gondii, and proteins such as indoleamine 2,3-dioxygenase that catabolize the breakdown of nutrients essential for parasite growth. In contrast, a new family of interferon-y-regulated effector proteins-the p47 GTPases-has recendy been iden tified that employ a much different mechanism to suppress T. gondii growth in activated mac rophages. Current theories suggest that the p47 GTPases traffick from intracellular membrane compartments to the T gondii vacuole, where they modulate processing of the vacuole, eventu ally undermining the integrity of the vacuole and survival o f the parasite. The essential role of p47 GTPases in controlling T. gondii is illustrated by mice that lack the proteins, and conse quently, are profoundly susceptible to acute infection. In this chapter, evidence is reviewed supporting the functions o f p47 GTPases and other effector proteins in macrophage-based control o f T. gondii.
