Malaria Biology and Genetics Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
Our laboratory focuses on the pre-erythrocytic phase of malaria. This phase extends from injection of the parasite in the skin by the mosquito vector to the onset of red blood cell infection, which causes the clinical symptoms of the disease. Our major aim is a functional understanding of the important host-parasite interactions that occur during the parasite journey to the liver, as well as inside hepatocytes. For this, we use a combination of molecular genetics, cell biology and in vivo imaging approaches. Another area of interest of our laboratory is to understand how the host can mount a protective immune response against this phase of Plasmodium infection. Indeed it has long been known that protection against the pre-erythrocytic stages of Plasmodium, unlike against other stages of the parasite can be sterilizing and long-lasting. We use rodent Plasmodium models of infection in our studies.
Contribution to the programme
Pre-erythrocytic infection can be prevented by injection of live attenuated sporozoites (traditionally irradiated sporozoites, IS), the parasite stage inoculated by mosquitoes. Our goal is to understand how and why attenuated sporozoites induce protective immunity, and particularly the parasite developmental stages/forms of the immunizing parasites that cause protection. Because our previous work has revealed that the PE phase of malaria involves sporozoites going to the liver but also staying in the skin or reaching its draining lymph node, our main aim will be to investigate the protection mounted by immunizing mice with WT sporozoites, IS or sporozoite mutants deficient in various steps of the infectious process to understand the ‘infection correlates’ of protection. We will also investigate the host immune cells in the skin and draining lymph node that are important for mounting a protective immune response after immunization in the skin.
References over the past 5 years
Amino R, Thiberge S, Blazquez S, Baldacci P, Renaud O, Shorte S, Ménard R. 2007. Imaging malaria sporozoites in the dermis of the mammalian host. Nature Protocols 2, 1705-1712.
Amino R, Giovannini D, Thiberge S, Gueirard P, Dubremetz JF, Prévost MC, Ishino T, Yuda M, Ménard R. 2008. Host cell traversal is important for progression of the malaria parasite from the dermis to the liver. Cell Host & Microbe 3, 88-96.
Ménard R, Heussler V, Yuda M, Nussenzweig V. 2008. Plasmodium pre-erythrocytic stages : what’s new ? Trends in Parasitology 24, 564-569.
Gonzalez V, Combe A, David V, Malmquist NA, Delorme V, Leroy C, Blazquez S, Ménard R, Tardieux I. 2009. Host cell entry by apicomplexa parasites requires actin polymerization in the host cell. Cell Host & Microbe 19, 259-272.
Combe A, Giovannini D, Carvalho TG, Spath S, Boisson B, Loussert C, Thiberge S, Lacroix C, Gueirard P, Ménard R. 2009. Clonal conditional mutagenesis in malaria parasites. Cell Host & Microbe 5, 386-396.
Gueirard P, Tavares J, Thiberge S, Bernex F, Ishino T, Milon G, Franke-Fayard B, Janse CJ, Ménard R, Amino R. 2010. Development of the malaria parasite in the skin of the mammalian host. Proceedings of National Academy of Sciences USA107, 18640-18645.
Giovannini D, Spaeth S, Lacroix C, Perazzi A, Bargieri D, Lagal V, Lebugle C, Combe A, Thiberge S, Baldacci P, Tardieux I, Ménard R. 2011. Independent roles of AMA1 and RON4 in distinct steps of host cell invasion by Apicomplexa. Cell Host & Microbe 10, 591-602.