title: Host cell traversal is important for progression of the malaria parasite through the dermis to the liver.
abstract: The malaria sporozoite, the parasite stage transmitted by the mosquito, is delivered into the dermis and differentiates in the liver. Motile sporozoites can invade host cells by disrupting their plasma membrane and migrating through them (termed cell traversal), or by forming a parasite-cell junction and settling inside an intracellular vacuole (termed cell infection). Traversal of liver cells, observed for sporozoites in vivo, is thought to activate the sporozoite for infection of a final hepatocyte. Here, using Plasmodium berghei, we show that cell traversal is important in the host dermis for preventing sporozoite destruction by phagocytes and arrest by nonphagocytic cells. We also show that cell infection is a pathway that is masked, rather than activated, by cell traversal. We propose that the cell traversal activity of the sporozoite must be turned on for progression to the liver parenchyma, where it must be switched off for infection of a final hepatocyte.
authors.affiliation: Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 28 Rue du Dr Roux, 75724 Paris cedex 15, France.
authors.forename: Rogerio
authors.initials: R
authors.lastname: Amino
authors.forename: Donatella
authors.initials: D
authors.lastname: Giovannini
authors.forename: Sabine
authors.initials: S
authors.lastname: Thiberge
authors.forename: Pascale
authors.initials: P
authors.lastname: Gueirard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Boisson
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prévost
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishino
authors.forename: Masao
authors.initials: M
authors.lastname: Yuda
authors.forename: Robert
authors.initials: R
authors.lastname: Ménard
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D002465:Cell Movement; D002478:Cells, Cultured; D020405:Dermis / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000469:parasitology; D010962:Plasmodium berghei / Q000737:chemistry / Q000378:metabolism* / Q000472:pathogenicity*; D017354:Point Mutation; D052899:Pore Forming Cytotoxic Proteins; D015800:Protozoan Proteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar / Q000469:parasitology; D034101:Sporozoites / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D014774:Virulence
chemical_list: D052899:Pore Forming Cytotoxic Proteins; D015800:Protozoan Proteins; C510153:SPECT protein, Plasmodium berghei; C503442:spect2 protein, Plasmodium berghei