title: Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells.
abstract: Malaria infection is initiated when Anopheles mosquitoes inject Plasmodium sporozoites into the skin. Sporozoites subsequently reach the liver, invading and developing within hepatocytes. Sporozoites contact and traverse many cell types as they migrate from skin to liver; however, the mechanism by which they switch from a migratory mode to an invasive mode is unclear. Here, we show that sporozoites of the rodent malaria parasite Plasmodium berghei use the sulfation level of host heparan sulfate proteoglycans (HSPGs) to navigate within the mammalian host. Sporozoites migrate through cells expressing low-sulfated HSPGs, such as those in skin and endothelium, while highly sulfated HSPGs of hepatocytes activate sporozoites for invasion. A calcium-dependent protein kinase is critical for the switch to an invasive phenotype, a process accompanied by proteolytic cleavage of the sporozoite's major surface protein. These findings explain how sporozoites retain their infectivity for an organ that is far from their site of entry.
authors.affiliation: Department of Medical Parasitology, 341 East 25th Street, New York University School of Medicine, New York, NY 10010, USA.
authors.forename: Alida
authors.initials: A
authors.lastname: Coppi
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Bennett
authors.forename: Roger
authors.initials: R
authors.lastname: Lawrence
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
authors.forename: Photini
authors.initials: P
authors.lastname: Sinnis
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D010962:Plasmodium berghei / Q000378:metabolism* / Q000472:pathogenicity; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014774:Virulence
chemical_list: D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins