A key feature of Toxoplasma gondii infection is the parasite's ability to manipulate biological pathways within its host. Previous research has demonstrated that T. gondii induces dendritic cells (DCs), the gatekeepers of the immune system, to become hypermigratory, but the molecular basis for this has remained poorly understood. Now, Antonio Barragan and colleagues (Ólafsson et al., 2019) use gene silencing and protein inhibition techniques to shed light on the signalling pathways involved in DC hypermigration upon infection by T. gondii. They reveal that transcription and secretion of TIMP-1, a protein previously associated with migration of cancer cells, is upregulated following T. gondii infection. Silencing of TIMP-1, or its binding partner CD63, results in decreased DC motility upon T. gondii challenge. Furthermore, inhibition of the previously identified TIMP-1—CD63 target ITGB1, and ITGB1's downstream effectors FAK, SRC and PI3K, also leads to reduced DC motility following Toxoplasma infection. The authors conclude that T. gondii probably modifies DC motility by regulating the TIMP-1—CD63—ITGB1—FAK signalling cascade. These findings provide important mechanistic insight into how T. gondii hijacks cellular pathways to disseminate within the host organism.
