Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Plasmodium sporozoites penetrate and migrate through multiple cells in the host before productively invading a hepatocyte and forming a parasitophorous vacuole. In this issue of Cell Host & Microbe, Coppi and colleagues show that sporozoite interaction with the highly sulfated heparan sulfate proteoglycans on liver cells induces proteolytic cleavage of the major sporozoite surface molecule. They conclude that this interaction is the primary trigger that activates sporozoites for productive invasion.