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Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity
被引:244
作者:
Silvie, O
Rubinstein, E
Franetich, JF
Prenant, M
Belnoue, E
Rénia, L
Hannoun, L
Eling, W
Levy, S
Boucheix, C
Mazier, D
机构:
[1] Univ Paris 11, Hop Paul Brousse, INSERM, U268,Inst Andre Lwoff, Villejuif, France
[2] Univ Paris 05, Hop Cochin, Inst Cochin, Dept Immunol, Paris, France
[3] Hop La Pitie Salpetriere, Serv Chirurg Digest Hepatobiliopancreat & Transpl, Paris, France
[4] Univ Med Ctr St Radboud, Dept Med Microbiol, Nijmegen, Netherlands
[5] Stanford Univ, Med Ctr, Dept Med, Div Oncol, Stanford, CA 94305 USA
关键词:
D O I:
10.1038/nm808
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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(1). 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(2), 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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页码:93 / 96
页数:4
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