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Elife. 2017 May 16;6. pii: e25903. doi: 10.7554/eLife.25903.

Plasmodium P36 determines host cell receptor usage during sporozoite invasion.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Paris, France.
2
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
3
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
4
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
5
Université de Strasbourg, Strasbourg, France.
6
Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institute of Cardiometabolism and Nutrition, UMR_S 1166, Paris, France.
7
INSERM, U935, Villejuif, France.
8
Université Paris Sud, Institut André Lwoff, Villejuif, France.
9
Assistance Publique Hôpitaux de Paris, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Paris, France.
10
Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hopitaux Universitaires de Strasbourg, Strasbourg, France.

Abstract

Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. Here we show that the two main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR-BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil redundant functions during infection by the rodent parasite P. berghei. Genetic analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a major parasite determinant of host cell receptor usage. Our data provide molecular insights into the invasion pathways used by different malaria parasites to infect hepatocytes, and establish a functional link between a sporozoite putative ligand and host cell receptors.

KEYWORDS:

P. berghei; P. falciparum; P. vivax; P. yoelii ; hepatocyte; human; infectious disease; malaria; microbiology; mouse; sporozoite

PMID:
28506360
PMCID:
PMC5470872
DOI:
10.7554/eLife.25903
[Indexed for MEDLINE]
Free PMC Article

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