1. Microbiology and Infectious Disease
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Plasmodium P36 determines host cell receptor usage during sporozoite invasion

  1. Giulia Manzoni
  2. Carine Marinach
  3. Selma Topçu
  4. Sylvie Briquet
  5. Morgane Grand
  6. Matthieu Tolle
  7. Marion Gransagne
  8. Julien Lescar
  9. Chiara Andolina
  10. Jean-François Franetich
  11. Mirjam B Zeisel
  12. Thierry Huby
  13. Eric Rubinstein
  14. Georges Snounou
  15. Dominique Mazier
  16. François Nosten
  17. Thomas F Baumert
  18. Olivier Silvie  Is a corresponding author
  1. Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, France
  2. Mahidol University, Thailand
  3. INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, France
  4. Sorbonne Universités, UPMC Univ Paris 06, INSERM, France
  5. INSERM, U935, France
  6. Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, France
Research Article
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Cite this article as: eLife 2017;6:e25903 doi: 10.7554/eLife.25903

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

  1. Giulia Manzoni

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Carine Marinach

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Selma Topçu

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Sylvie Briquet

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Morgane Grand

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthieu Tolle

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Marion Gransagne

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Julien Lescar

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Chiara Andolina

    Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  10. Jean-François Franetich

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Mirjam B Zeisel

    INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Thierry Huby

    Institute of Cardiometabolism and Nutrition, UMR_S 1166, Sorbonne Universités, UPMC Univ Paris 06, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6634-551X
  13. Eric Rubinstein

    INSERM, U935, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7623-9665
  14. Georges Snounou

    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Dominique Mazier

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  16. François Nosten

    Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7951-0745
  17. Thomas F Baumert

    INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourgf, France
    Competing interests
    The authors declare that no competing interests exist.
  18. Olivier Silvie

    Centre d'Immunologie et des Maladies Infectieuses, U1135, ERL8255, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    For correspondence
    olivier.silvie@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0525-6940

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

  1. Elena Levashina, Max Planck Institute for Infection Biology, Germany

Publication history

  1. Received: February 9, 2017
  2. Accepted: May 10, 2017
  3. Accepted Manuscript published: May 16, 2017 (version 1)
  4. 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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