Mechanism of Toxoplasma gondii dissemination using immune cells as a shuttle carriers

Toxoplasma gondii has developed efficient mechanisms to disseminate within the host, reaching virtually any tissue including immunoprivileged sites like the eye and the brain. This wide distribution is achieved by using migratory immune cells as shuttle carriers. Migratory immune cells are specialised in navigation, travelling long distances and crossing complex biological barriers, to reach any cell in the host. However, using immune cells as dissemination mechanism involves a complex balance between maintaining parasite replication and migratory fitness of the infected immune cell, which is bearing an increasing large cargo. Although molecular biological data on Toxoplasma -cell hijacking are well studied, the biophysical mechanisms underneath the trojan-horse migration are unresolved. Here, using advance microscopy techniques, custom-designed microchannels, 3D matrices and parasite and immune cell mutants we investigate the biophysical principles of locomotion of immune cells with parasite cargo. Our results show that infected immune cells are able to maintain migration, path finding and navigation properties through extraordinarily tight constrictions. Under extreme cell deformation, caused by crossing narrow and rigid constrictions, host-Toxoplasma adaptations show a dynamic actin network surrounded by a cage-like host microtubule network that ensure optimal balance between host migratory properties and mechanical resilience of the parasitophorous vacuole.