Role of host cell traversal by the malaria sporozoite during liver infection

Joana Tavares, Pauline Formaglio, Sabine Thiberge, Elodie Mordelet, Nico Van Rooijen, Alexander Medvinsky, Robert Ménard, Rogerio Amino*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Malaria infection starts when the sporozoite stage of the Plasmodium parasite is injected into the skin by a mosquito. Sporozoites are known to traverse host cells before finally invading a hepatocyte and multiplying into erythrocyte-infecting forms, but how sporozoites reach hepatocytes in the liver and the role of host cell traversal (CT) remain unclear. We report the first quantitative imaging study of sporozoite liver infection in rodents. We show that sporozoites can cross the liver sinusoidal barrier by multiple mechanisms, targeting Kupffer cells (KC) or endothelial cells and associated or not with the parasite CT activity. We also show that the primary role of CT is to inhibit sporozoite clearance by KC during locomotion inside the sinusoid lumen, before crossing the barrier. By being involved in multiple steps of the sporozoite journey from the skin to the final hepatocyte, the parasite proteins mediating host CT emerge as ideal antibody targets for vaccination against the parasite.

Original languageEnglish
Pages (from-to)905-915
Number of pages11
JournalJournal of Experimental Medicine
Volume210
Issue number5
DOIs
Publication statusPublished - 1 May 2013

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