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Science 313 (5791): 1287-1290

Copyright © 2006 by the American Association for the Advancement of Science

Manipulation of Host Hepatocytes by the Malaria Parasite for Delivery into Liver Sinusoids

Angelika Sturm,1* Rogerio Amino,2,3* Claudia van de Sand,1 Tommy Regen,1 Silke Retzlaff,1 Annika Rennenberg,1 Andreas Krueger,1 Jörg-Matthias Pollok,4 Robert Menard,2 Volker T. Heussler1{dagger}

Abstract: The merozoite stage of the malaria parasite that infects erythrocytes and causes the symptoms of the disease is initially formed inside host hepatocytes. However, the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the liver and escape the host immune system before invading erythrocytes remains unknown. Here, we show that parasites induce the death and the detachment of their host hepatocytes, followed by the budding of parasite-filled vesicles (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the exposure of phosphatidylserine on the outer leaflet of host plasma membranes, which act as "eat me" signals to phagocytes. Thus, the hepatocyte-derived merosomes appear to ensure both the migration of parasites into the bloodstream and their protection from host immunity.

1 Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany.
2 Department of Parasitology, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
3 Department of Biochemistry, Federal University of Sao Paulo, Rua Tres de Maio, 04044-020, Sao Paulo, Brazil.
4 Department of Hepatobiliary Surgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: heussler{at}bni-hamburg.de

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