Heparan Sulfate Proteoglycans Provide a Signal to Plasmodium Sporozoites to Stop Migrating and Productively Invade Host Cells

Alida Coppi, Rita Tewari, Joseph R. Bishop, Brandy L. Bennett, Roger Lawrence, Jeffrey D. Esko, Oliver Billker, Photini Sinnis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)316-327
Number of pages12
JournalCell Host and Microbe
Volume2
Issue number5
DOIs
StatePublished - Nov 15 2007

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Keywords

  • CELLBIO
  • MICROBIO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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