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

TitleRole of host cell traversal by the malaria sporozoite during liver infection.
Publication TypeJournal Article
Year of Publication2013
AuthorsTavares J, Formaglio P, Thiberge S, Mordelet E, van Rooijen N, Medvinsky AL, Ménard R, Amino R
JournalJ Exp Med
Volume210
Issue5
Pagination905-15
Date Published2013 May 6
ISSN1540-9538
KeywordsAnimals, Anopheles, Cell Death, Cell Movement, Endothelial Cells, Female, Green Fluorescent Proteins, Host-Parasite Interactions, Kupffer Cells, Liver, Malaria, Male, Mice, Mice, Inbred C57BL, Plasmodium berghei, Sporozoites
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.

DOI10.1084/jem.20121130
Alternate JournalJ. Exp. Med.
PubMed ID23610126
PubMed Central IDPMC3646492
Grant ListG0900962 / / Medical Research Council / United Kingdom
Publication institute
CRM