title: Expression of human CD81 differently affects host cell susceptibility to malaria sporozoites depending on the Plasmodium species.
abstract: Plasmodium sporozoites can enter host cells by two distinct pathways, either through disruption of the plasma membrane followed by parasite transmigration through cells, or by formation of a parasitophorous vacuole (PV) where the parasite further differentiates into a replicative exo-erythrocytic form (EEF). We now provide evidence that following invasion without PV formation, transmigrating Plasmodium falciparum and Plasmodium yoelii sporozoites can partially develop into EEFs inside hepatocarcinoma cell nuclei. We also found that rodent P. yoelii sporozoites can infect both mouse and human hepatocytes, while human P. falciparum sporozoites infect human but not mouse hepatocytes. We have previously reported that the host tetraspanin CD81 is required for PV formation by P. falciparum and P. yoelii sporozoites. Here we show that expression of human CD81 in CD81-knockout mouse hepatocytes is sufficient to confer susceptibility to P. yoelii but not P. falciparum sporozoite infection, showing that the narrow P. falciparum host tropism does not rely on CD81 only. Also, expression of CD81 in a human hepatocarcinoma cell line is sufficient to promote the formation of a PV by P. yoelii but not P. falciparum sporozoites. These results highlight critical differences between P. yoelii and P. falciparum sporozoite infection, and suggest that in addition to CD81, other molecules are specifically required for PV formation during infection by the human malaria parasite.
authors.affiliation: Inserm, U511, F-75013 Paris, France; Université Pierre et Marie Curie-Paris 6, Faculté de Médecine Pitié-Salpêtrière, F-75013 Paris, France. silvie@ext.jussieu.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Silvie
authors.forename: Céline
authors.initials: C
authors.lastname: Greco
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.forename: Anne
authors.initials: A
authors.lastname: Dubart-Kupperschmitt
authors.forename: Laurent
authors.initials: L
authors.lastname: Hannoun
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.forename: Eric
authors.initials: E
authors.lastname: Rubinstein
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000469:parasitology / Q000648:ultrastructure; D006790:Host-Parasite Interactions; D006801:Humans; D051379:Mice; D010963:Plasmodium falciparum / Q000254:growth & development / Q000472:pathogenicity*; D010967:Plasmodium yoelii / Q000254:growth & development / Q000472:pathogenicity*; D013045:Species Specificity; D034101:Sporozoites / Q000472:pathogenicity*; D060225:Tetraspanin 28
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D060225:Tetraspanin 28