title: Malaria parasites target the hepatocyte receptor EphA2 for successful host infection.
abstract: 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.
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. alexis.kaushansky@cidresearch.org stefan.kappe@cidresearch.org.
authors.forename: Alexis
authors.initials: A
authors.lastname: Kaushansky
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA.
authors.forename: Alyse N
authors.initials: AN
authors.lastname: Douglass
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Arang
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vigdorovich
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dambrauskas
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Kain
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Austin
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA.
authors.forename: D Noah
authors.initials: DN
authors.lastname: Sather
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98195, USA. alexis.kaushansky@cidresearch.org stefan.kappe@cidresearch.org.
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000201:enzymology* / Q000469:parasitology*; D006801:Humans; D008288:Malaria / Q000201:enzymology* / Q000235:genetics / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010961:Plasmodium / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism*; D036104:Receptor, EphA2 / Q000235:genetics / Q000378:metabolism*; D034101:Sporozoites / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; D036104:Receptor, EphA2