T. gondii grows within a parasitophorous vacuole membrane (PVM) that protects the parasite from cytosolic immune sensors and avoids fusion with the endolysosomal compartments containing Toll-like receptors (TLRs). In the mouse, TLR11 recognizes Tg profilin, an actin-modifying protein that is exposed once dead or damaged parasites are phagocytosed. TLR11 is a pseudogene in humans. TgGRA15 can promote host NF-κB phosphorylation and nuclear translocation. In mice, NF-κB stimulation is necessary for transcriptional regulation of the inflammasome components NLRP1, NLRP3, and IL-1; however, human monocytes can engage an NLRP3 inflammasome independent of NF-κB prestimulation. A detailed mechanism of inflammasome activation, parasite killing, and host cell death remains elusive, particularly in regard to signal integration with IFN-γ. IFN-γ signaling induces STAT1 translocation to the nucleus and upregulation of IFN-responsive genes, including immunity-related GTPases (IRGs, mouse) and guanylate-binding proteins (GBPs, human and mouse), which functions to attack parasite vacuole, leading to parasite killing and host cell death. In human cells, GBP1 is necessary for this process, which leads to AIM2 activation of an alternative apoptosis pathway. The type I parasite rhoptry proteins, TgROP5, 17, and 18, can dismantle the function of the mouse IRGs IRGa6 and IRGb6 at the PVM, inactivating GBP attack and parasite killing. The parasite dense granule effector TgIST is a nuclear repressor of STAT1 transcription. TgROP16 is a kinase that phosphorylates and activates host STAT3 and STAT6. TgEGGR affects host gene expression through E2F3- and E2F4-mediated epigenetic modifications. In infected monocytes and dendritic cells (DCs), TgWIP and 14-3-3 proteins promote cell mobility, a putative mechanism of intracellular parasite dissemination in vivo.