Nature Medicine9, 93 - 96 (2002)
Published online: 16 December 2002; | doi:10.1038/nm808
Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity
Olivier Silvie1, Eric Rubinstein2, Jean-François Franetich1, Michel Prenant2, Elodie Belnoue3, Laurent Rénia3, Laurent Hannoun4, Wijnand Eling5, Shoshana Levy6, Claude Boucheix2, 7
& Dominique Mazier1, 7
1
INSERM U511 Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France
2
INSERM U268 Institut André-Lwoff, Université Paris XI, Hôpital Paul-Brousse, Villejuif, France
3
Département d'Immunologie, Institut Cochin, Université René Descartes, Hôpital Cochin, Paris, France
4
Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, Paris, France
5
Department of Medical Microbiology, University Medical Centre St. Radboud, Nijmegen, The Netherlands
6
Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, California, USA
7
C.B. and D.M. contributed equally to this study.
Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and first invade the liver of the mammalian host, as an obligatory step of the life cycle of the malaria parasite. Within hepatocytes, Plasmodium sporozoites reside in a membrane-bound vacuole, where they differentiate into exoerythrocytic forms and merozoites that subsequently infect erythrocytes and cause the malaria disease. Plasmodium sporozoite targeting to the liver is mediated by the specific binding of major sporozoite surface proteins, the circumsporozoite protein and the thrombospondin-related anonymous protein, to glycosaminoglycans on the hepatocyte surface1. Still, the molecular mechanisms underlying sporozoite entry and differentiation within hepatocytes are largely unknown. Here we show that the tetraspanin CD81, a putative receptor for hepatitis C virus2, is required on hepatocytes for human Plasmodium falciparum and rodent Plasmodium yoelii sporozoite infectivity. P. yoelii sporozoites fail to infect CD81-deficient mouse hepatocytes, in vivo and in vitro, and antibodies against mouse and human CD81 inhibit in vitro the hepatic development of P. yoelii and P. falciparum, respectively. We further demonstrate that the requirement for CD81 is linked to sporozoite entry into hepatocytes by formation of a parasitophorous vacuole, which is essential for parasite differentiation into exoerythrocytic forms.
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