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NK Cell Responses to Plasmodium Infection and Control of Intrahepatic Parasite Development¹

Jacques Roland^2,*, Valérie Soulard^*, Christèle Sellier^*, Anne-Marie Drapier^*, James P. Di Santo, Pierre-André Cazenave^* and Sylviane Pied^*

^* Unité d’Immunophysiopathologie Infectieuse, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Université Pierre et Marie Curie, Institut Pasteur, Paris, France; and Unité des Cytokines et Développement Lymphoïde, Institut National de la Santé et de la Recherche Médicale U 668, Institut Pasteur, Paris, France

Various components of innate and adaptive immunity contribute to host defenses against Plasmodium infection. We investigated the contribution of NK cells to the immune response to primary infection with Plasmodium yoelii sporozoites in C57BL/6 mice. We found that hepatic and splenic NK cells were activated during infection and displayed different phenotypic and functional properties. The number of hepatic NK cells increased whereas the number of splenic NK cells decreased. Expression of the Ly49 repertoire was modified in the spleen but not in the liver. Splenic and hepatic NK cells have a different inflammatory cytokines profile production. In addition, liver NK cells were cytotoxic to YAC-1 cells and P. yoelii liver stages in vitro but not to erythrocytic stages. No such activity was observed with splenic NK cells from infected mice. These in vitro results were confirmed by the in vivo observation that Rag2^–/– mice were more resistant to sporozoite infection than Rag2^–/– c^–/– mice, whereas survival rates were similar for the two strains following blood-stage infection. Thus, NK cells are involved in early immune mechanisms controlling Plasmodium infection, mostly at the pre-erythrocytic stage.

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