title: Malaria Sporozoites Traverse Host Cells within  Transient Vacuoles.
abstract: Plasmodium sporozoites are deposited in the host skin by Anopheles mosquitoes. The parasites migrate from the dermis to the liver, where they invade hepatocytes through a moving junction (MJ) to form a replicative parasitophorous vacuole (PV). Malaria sporozoites need to traverse cells during progression through host tissues, a process requiring parasite perforin-like protein 1 (PLP1). We find that sporozoites traverse cells inside transient vacuoles that precede PV formation. Sporozoites initially invade cells inside transient vacuoles by an active MJ-independent process that does not require vacuole membrane remodeling or release of parasite secretory organelles typically involved in invasion. Sporozoites use pH sensing and PLP1 to exit these vacuoles and avoid degradation by host lysosomes. Next, parasites enter the MJ-dependent PV, which has a different membrane composition, precluding lysosome fusion. The malaria parasite has thus evolved different strategies to evade host cell defense and establish an intracellular niche for replication.
authors.forename: Veronica
authors.initials: V
authors.lastname: Risco-Castillo
authors.forename: Selma
authors.initials: S
authors.lastname: Topçu
authors.forename: Carine
authors.initials: C
authors.lastname: Marinach
authors.forename: Giulia
authors.initials: G
authors.lastname: Manzoni
authors.forename: Amélie E
authors.initials: AE
authors.lastname: Bigorgne
authors.forename: Sylvie
authors.initials: S
authors.lastname: Briquet
authors.forename: Xavier
authors.initials: X
authors.lastname: Baudin
authors.forename: Maryse
authors.initials: M
authors.lastname: Lebrun
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
authors.forename: Olivier
authors.initials: O
authors.lastname: Silvie
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008288:Malaria / Q000469:parasitology* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D010967:Plasmodium yoelii / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000378:metabolism; D034101:Sporozoites / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology*; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology* / Q000648:ultrastructure
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins