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

Valérie Soulard (1) , Henriette Bosson-Vanga (1, 2) , Audrey Lorthiois (1) , Clémentine Roucher (1) , Jean-François Franetich (1) , Gigliola Zanghi (1) , Mallaury Bordessoulles (1) , Maurel Tefit (1) , Marc Thellier (3, 3) , Serban Morosan (4) , Gilles Le Naour (3) , Frédérique Capron (3) , Hiroshi Suemizu (5) , Georges Snounou (1) , Alicia Moreno-Sabater (1) , Dominique Mazier (1, 3, 3)

1 CIMI - Centre d'Immunologie et de Maladies Infectieuses
2 Departement de Parasitologie-Mycologie
3 CHU Pitié-Salpêtrière [AP-HP]
4 UMS28 - Phénotypage du petit animal
5 Central Institute for Experimental Animal

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.

Domains: Biochemistry, Molecular Biology

Valérie Soulard, Henriette Bosson-Vanga, Audrey Lorthiois, Clémentine Roucher, Jean-François Franetich, et al.. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice.. Nature Communications, 2015, 6, pp.7690. ⟨10.1038/ncomms8690⟩. ⟨inserm-01207321⟩