Exposing the hidden: establishing immunity to Plasmodium liver stage infection

Plasmodium, the parasite which causes malaria, has evolved with - and plagued - humans since our species emerged. Decades of intervention efforts have concluded that the blueprint for success is to hamper transmission between Anopheles mosquitoes and humans. Before causing symptomatic blood-stage infection, Plasmodium must first develop in the liver, which serves as a hidden gateway into the human host. Blocking parasite entrance or exit through the liver stage prevents both illness and onward transmission. Robust immunity against the pre-erythrocytic stages of Plasmodium falciparum fails to develop during natural exposure in malaria-endemic countries. Here, we highlight how expanding knowledge of key mechanisms involved in the immune response against the liver stage parasite is shaping current and future intervention strategies against malaria.