Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity
Autor: | Michel Prenant, Claude Boucheix, Wijnand Eling, Elodie Belnoue, Dominique Mazier, Jean-François Franetich, Olivier Silvie, Laurent Rénia, Laurent Hannoun, Shoshana Levy, Eric Rubinstein |
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Rok vydání: | 2003 |
Předmět: |
Recombinant Fusion Proteins
Plasmodium falciparum Protozoan Proteins Vacuole Plasmodium Tetraspanin 29 General Biochemistry Genetics and Molecular Biology Tetraspanin 28 Mice Antigens CD Anopheles parasitic diseases medicine Animals Humans Malaria Falciparum Cells Cultured Mice Knockout Infectivity Mice Inbred BALB C Membrane Glycoproteins biology Membrane Proteins Plasmodium yoelii General Medicine biology.organism_classification Virology Malaria Mice Inbred C57BL Circumsporozoite protein medicine.anatomical_structure Sporozoites Hepatocyte Hepatocytes Microbial pathogenesis and host defense [UMCN 4.1] CD81 |
Zdroj: | Nature Medicine, 9, 1, pp. 93-6 Nature Medicine, 9, 93-6 |
ISSN: | 1078-8956 |
Popis: | Item does not contain fulltext 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 surface. 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 virus, 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. |
Databáze: | OpenAIRE |
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