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Innate immunity to malaria liver infection and reinfection

Vendredi 11 décembre 2015 14:00 - Duree : 1 heure
Lieu : LAPM, Institut Jean Roget, Salle de Conférence du 5ème Etage, Faculté de Médecine-Pharmacie, Domaine de la Merci, La Tronche

Orateur : Peter LIEHL (International Center for Research on Infectious Diseases, INSERM U 1111 – CNRS UMR 5308 University of Lyon I –ENS Lyon – Institute of Functional Genomics of Lyon)

Malaria, caused by the protozoan parasite Plasmodium, is one of the most prevalent infectious diseases worldwide. Before infecting red blood cells and causing malaria, Plasmodium parasites undergo an obligate and clinically silent expansion phase in the liver that has long been thought to remain undetected by the host. Transcriptomic analysis of whole livers from infected mice allowed us to identify the genes induced during Plasmodium liver infection. We made the striking discovery that the liver innate immune system responds to infection by engaging a type I IFN response during Plasmodium replication in the liver. Combined genetics and molecular biology approaches further indicated that the sensing mechanism depends on the intracellular pattern recognition receptor MDA5 that recognizes Plasmodium RNA. This constitutes the first non-viral ligand described for MDA5. We also demonstrated that the pathway further involves signaling from the adaptor molecule MAVS and the transcription factors IRF3 and IRF7. Our results suggest a model in which the activation of this cytosolic signaling pathway leads to the release of type I IFNs into the extracellular environment where it binds to type I IFN receptor IFNAR on hepatocytes, propagating the response in an auto- and paracrine manner throughout the liver. Our data showed that the type I IFN-driven response is involved in host resistance against Plasmodium infection. We found that the hepatocyte type I IFN response itself is not sufficient to eliminate the parasite, but the hepatocyte-mediated propagation of the response, after the initial sensing events, is critical to recruit and activate the innate immune cells required for parasite elimination. Lastly, our data demonstrate that the type I IFN driven response is functionally relevant for host resistance against a primary Plasmodium liver stage infection and malaria reinfection.

Contact : cordelia.bisanz@ujf-grenoble.fr

Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (LAPM)
Nature évènement : (Séminaire)
Evènement répétitif : (Séminaire IJR)
Site de l'évènement : Pôle Santé / La Tronche

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