%0 Journal Article %T Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite %+ Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions %+ Collège Doctoral %+ Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS) %+ Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology %+ Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB) %+ Goldyne Savad Institute of Gene Therapy %+ University of Bern %+ Infection et Immunité paludéennes - Malaria Infection and Immunity %A Grand, Morgane %A Waqasi, Mishelle %A Demarta-Gatsi, Claudia %A Wei, Yu %A Peronet, Roger %A Commere, Pierre-Henri %A Puig, Amandine %A Axelrod, Jonathan %A Caldelari, Reto %A Heussler, Volker %A Amino, Rogerio %A Mecheri, Salaheddine %Z This work has been supported by the French Parasitology consortium ParaFrap (ANR-11-LABX0024), and by a grant from Institut Pasteur to MG, and SM. CD-G was supported by a postdoctoral fellowship from the Helmut Horten Foundation, Agno, Switzerland. %< avec comité de lecture %@ 1664-3224 %J Frontiers in Immunology %I Frontiers %V 11 %P 585502 %8 2020-11-19 %D 2020 %R 10.3389/fimmu.2020.585502 %M 33329563 %K CD8-CD4 T cells %K inflammation %K liver %K malaria %K vaccine %Z Life Sciences [q-bio]Journal articles %X Deciphering the mechanisms by which Plasmodium parasites develop inside hepatocytes is an important step toward the understanding of malaria pathogenesis. We propose that the nature and the magnitude of the inflammatory response in the liver are key for the establishment of the infection. Here, we used mice deficient in the multidrug resistance-2 gene (Mdr2-/-)-encoded phospholipid flippase leading to the development of liver inflammation. Infection of Mdr2-/- mice with Plasmodium berghei ANKA (PbANKA) sporozoites (SPZ) resulted in the blockade of hepatic exo-erythrocytic forms (EEFs) with no further development into blood stage parasites. Interestingly, cultured primary hepatocytes from mutant and wild-type mice are equally effective in supporting EEF development. The abortive infection resulted in a long-lasting immunity in Mdr2-/- mice against infectious SPZ where neutrophils and IL-6 appear as key effector components along with CD8+ and CD4+ effector and central memory T cells. Inflammation-induced breakdown of liver tolerance promotes anti-parasite immunity and provides new approaches for the design of effective vaccines against malaria disease. %G English %2 https://pasteur.hal.science/pasteur-03255314/document %2 https://pasteur.hal.science/pasteur-03255314/file/fimmu-11-585502.pdf %L pasteur-03255314 %U https://pasteur.hal.science/pasteur-03255314 %~ INSERM %~ PASTEUR %~ RIIP %~ CNRS %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-TI %~ ANR %~ ALLIANCE-SU %~ BIOLOGY-HOST-PARASITE-INTERACTIONS