Updated project metadata. The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for systemic dissemination. We report that, upon T. gondii infection, macrophages initiate expression of transcription factors normally attributed to DCs, upregulate the expression of Ccr7 with a chemotactic response, and perform systemic migration when adoptively transferred into mice. We identify the parasite effector GRA28, which is secreted into the host cell nuclei, as driving the chemotactic migratory activation of parasitized macrophages. To gain insight about the molecular role played by GRA28 in this phenomenon, we characterized its interactome.