Malaria parasites target the hepatocyte receptor EphA2 for successful host infection

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Science  27 Nov 2015:
Vol. 350, Issue 6264, pp. 1089-1092
DOI: 10.1126/science.aad3318

How malaria parasites infect the liver

Early in infection, malaria parasites establish themselves within hepatocytes in the liver. Inside these cells, the parasites occupy a so-called parasitophorous vacuole. Kaushansky et al. show that malaria parasites prefer to create vacuoles within hepatocytes that express the EphA2 receptor. Hepatocytes with low levels of this receptor were less conducive to malaria infection.

Science, this issue p. 1089


The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment.

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