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

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

doi:10.1038/ncomms8690

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.

Highlights

Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity
Liverhumanized (LH) TK-NOG mice were inoculated with 1–3 million P. falciparum sporozoites, killed at different time points thereafter, and their livers were analysed for the presence of parasites by immunofluorescent staining of Plasmodium HSP70 (Fig. 1a)
We confirmed that the parasites developed exclusively in the engrafted human hepatocytes (hHEP) stained for Human albumin (hAlb) (Supplementary Fig. 2)

Summary

Introduction

Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Plasmodium sporozoites injected by an infected mosquito migrate to the liver and initiate the hepatic stage of the parasite life cycle by invading hepatocytes within which they multiply and differentiate into schizonts containing thousands of hepatic merozoites. These merozoites are subsequently released into the blood where they initiate the erythrocytic stage by invading and replicating within red blood cells (RBCs). The major interest in these hepatic forms is that they represent the initial obligatory phase of the life cycle of Plasmodium in the human host During this pre-erythrocytic phase the parasites are present in very low numbers and generally develop over a short period (5–14 days). This makes them an ideal target for parasite elimination[10]

Methods

Results

Conclusion