Malaria is caused by variants of Plasmodium parasites carried by mosquitoes, and remains a leading cause death worldwide. The strain Plasmodium falciparum triggers a very severe form of malaria, accounting for the majority of deaths. Those people infected with less virulent strain P.ovale may also suffer serious illness, but a key difference is that this particular strain has the ability to ‘lie dormant’ in the body only to reappear months, or even years, later.
Due to the parasites behaving differently in different hosts, it has proven difficult to study the parasites inside the body to verify their precise life-cycle and replication.
Now, for the first time, Valerie Soulard and co-workers at Sorbonne University, Paris, France, with an international team of scientists including Hiroshi Suemizu at the Central Institute for Experimental Animals, Kawasaki, have successfully analyzed the complete life cycle of P.falciparum in the bodies of humanized mice. They also uncovered the stages P.ovale parasites follow inside humanized mice liver cells.
Soulard and her team engrafted mice with both human liver tissues and human red blood cells, to follow the complete development of the P.falciparum parasites from early stages in liver cells, through multiplication to the appearance of mature germ cells in the blood stream.
In addition, the team discovered that, unlike P.falciparum, P.ovale parasites are able to ‘pause’ their development in the liver, maturing weeks later to trigger a relapse of the disease in the patient.
The team hope the further use of humanized mice for malarial studies will aid the routine validation of drugs and live vaccines for the disease, together with further analysis of Plasmodium strains.
Reference and affiliations
Valérie Soulard1,2,3, Henriette Bosson-Vanga1,2,3,4,*, Audrey Lorthiois1,2,3,*,w, Clémentine Roucher1,2,3, Jean- François Franetich1,2,3, Gigliola Zanghi1,2,3, Mallaury Bordessoulles1,2,3, Maurel Tefit1,2,3, Marc Thellier5, Serban Morosan6, Gilles Le Naour7, Frédérique Capron7, Hiroshi Suemizu8, Georges Snounou1,2,3, Alicia Moreno-Sabater1,2,3,* & Dominique Mazier1,2,3,5,*. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice. Nature Communications 6 (7690) Published 24 July 2015
- Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l’hôpital, F-75013 Paris, France.
- INSERM, U1135, CIMI-PARIS, 91 Bd de l’hôpital, F-75013 Paris, France.
- CNRS, ERL 8255, CIMI-PARIS, 91 Bd de l’hôpital, F-75013 Paris, France.
- Université FHB, UFR SPB, Departement de Parasitologie-Mycologie, BP V 34 Abidjan, Ivory Coast.
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service Parasitologie-Mycologie, Centre National de Référence du Paludisme, 83 Bd de l’hôpital, F-75013 Paris, France.
- UPMC Univ. Paris 06, INSERM, UMS28, 105 Bd de l’hôpital, F-75013 Paris, France.
- AP-HP, UPMC Univ. Paris 06, Groupe Hospitalier Pitié-Salpêtrière, Service d’anatomie et cytologie pathologiques, 83 Bd de l’hôpital, F-75013 Paris, France.
- Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
w Present address: INSERM U1016, CNRS UMRS 8104, Institut Cochin, F-75014 Paris, France.
*corresponding author email address: email@example.com
For the first time, researchers in France (with the help of the Central Institute for Experimental Animals, Kawasaki, Japan) have generated humanized mice engrafted with both human liver tissue and human red blood cells. The mice were then used to reveal the full life-cycle of Plasmodium falciparum, and liver stage life-cycle of Plasmodium ovale, two of the parasites that cause malaria.