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Malaria: new insights into the mechanisms of parasite entry into liver cells

16 May 2017 - 14h52 | By INSERM PRESS OFFICE | Immunology, inflammation, infectiology and microbiology

modele-p36

3D model of a Plasmodium protein mediating parasite entry into liver cells. ©O. Silvie

Malaria remains a major cause of mortality in the world, especially in Africa. The disease is caused by Plasmodium parasites, which are transmitted by mosquitoes. In the first hours following infection, parasites injected by the mosquito migrate from the skin to the liver, where they initially multiply before infecting red blood cells.

Until now, the mechanisms of parasite entry into liver cells remained poorly understood. Using cell culture systems, the team of Olivier Silvie, researcher at Inserm (Centre d’Immunologie et des Maladies Infectieuses) showed that the main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, use distinct pathways to infect liver cells.

By employing a genetic approach in a rodent malaria model, the researchers identified a key parasite protein that determines which entry route is used. This work, performed by teams of Inserm and Universities of Paris, Strasbourg and Oxford-Mahidol, reveals new aspects of the host-parasite interactions.

The results open new perspectives for the development of antimalarial strategies aimed at blocking the early stages of infection.

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Researcher Contact

Olivier Silvie

Inserm 1135 – Centre d’Immunologie et des Maladies Infectieuses – Paris

01.40.77.81.11

olivier.silvie@inserm.fr

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Plasmodium P36 determines host cell receptor usage during sporozoite invasion

Giulia Manzoni1, Carine Marinach1*, Selma Topçu1*, Sylvie Briquet1, Morgane Grand1, Matthieu Tolle1, Marion Gransagne1, Julien Lescar1, Chiara Andolina2,3, Jean-François Franetich1, Mirjam B. Zeisel4, Thierry Huby5, Eric Rubinstein6,7, Georges Snounou1, Dominique Mazier1,8, François Nosten2,3, Thomas F. Baumert4,9, Olivier Silvie1

 

1Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, U1135, ERL8255, F-75013, Paris, France.

2Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

3Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research building, University of Oxford Old Road campus, Oxford, United Kingdom.

4INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, F-67000, Strasbourg, France; Université de Strasbourg, F-67000, Strasbourg, France.

5Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institute of Cardiometabolism and Nutrition, UMR_S 1166, F-75013, Paris, France.

6INSERM, U935, F-94807, Villejuif, France.

7Université Paris Sud, Institut André Lwoff, F-94807, Villejuif, France.

8Assistance Publique Hôpitaux de Paris, Centre Hospitalo-Universitaire Pitié- Salpêtrière, F-75013 Paris, France.

9Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hopitaux Universitaires de Strasbourg, F-67000 Strasbourg, France.

 

*CM and ST contributed equally to this study

 

eLife, http://dx.doi.org/10.7554/eLife.25903

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