Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice

Valérie Soulard (), Henriette Bosson-Vanga, Audrey Lorthiois, Clémentine Roucher, Jean- François Franetich, Gigliola Zanghi, Mallaury Bordessoulles, Maurel Tefit, Marc Thellier, Serban Morosan, Gilles Le Naour, Frédérique Capron, Hiroshi Suemizu, Georges Snounou, Alicia Moreno-Sabater and Dominique Mazier
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Valérie Soulard: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Henriette Bosson-Vanga: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Audrey Lorthiois: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Clémentine Roucher: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Jean- François Franetich: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Gigliola Zanghi: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Mallaury Bordessoulles: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Maurel Tefit: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Marc Thellier: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service Parasitologie-Mycologie, Centre National de Référence du Paludisme
Serban Morosan: UPMC Univ. Paris 06, INSERM, UMS28
Gilles Le Naour: AP-HP, UPMC Univ. Paris 06, Groupe Hospitalier Pitié-Salpêtrière, Service d’anatomie et cytologie pathologiques
Frédérique Capron: AP-HP, UPMC Univ. Paris 06, Groupe Hospitalier Pitié-Salpêtrière, Service d’anatomie et cytologie pathologiques
Hiroshi Suemizu: Central Institute for Experimental Animal
Georges Snounou: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Alicia Moreno-Sabater: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Dominique Mazier: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans.

Date: 2015
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DOI: 10.1038/ncomms8690

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