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.
Article and author information
Author details
Funding
European Commission
- Dominique Mazier
- Thomas F Baumert
- Olivier Silvie
Agence Nationale de la Recherche
- Mirjam B Zeisel
- Dominique Mazier
- Thomas F Baumert
- Olivier Silvie
National Centre for the Replacement, Refinement and Reduction of Animals in Research
- Olivier Silvie
Conseil Régional, Île-de-France
- Giulia Manzoni
- Marion Gransagne
Wellcome
- François Nosten
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work was conducted in strict accordance with the Directive 2010/63/EU of the European Parliament and Council 'On the protection of animals used for scientific purposes'. The protocol was approved by the Charles Darwin Ethics Committee of the University Pierre et Marie Curie, Paris, France (permit number Ce5/2012/001).
Human subjects: Blood samples were obtained from P. vivax-infected individuals attending the Shoklo Malaria Research Unit (SMRU) clinics on the western Thailand-Myanmar border, after signature of a consent form. Primary human hepatocytes were isolated from healthy parts of human liver fragments, which were collected from adult patients undergoing partial hepatectomy (Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Groupe Hospitalier Pitie-Salpetriere, Paris, France). The collection and use of this material were undertaken in accordance with French national ethical guidelines under Article L. 1121-1 of the 'Code de la Santé Publique', and approved by the Institutional Review Board (Comité de Protection des Personnes) of the Centre Hospitalo-Universitaire Pitié-Salpetriere, Assistance Publique-Hopitaux de Paris, France.
Reviewing Editor
- Elena Levashina, Max Planck Institute for Infection Biology, Germany
Publication history
- Received: February 9, 2017
- Accepted: May 10, 2017
- Accepted Manuscript published: May 16, 2017 (version 1)
- Version of Record published: June 14, 2017 (version 2)
Copyright
© 2017, Manzoni et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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