%0 Journal Article %T Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite. %+ Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions %+ Biologie et Génétique du Paludisme %A Demarta-Gatsi, Claudia %A Peronet, Roger %A Smith, Leanna %A Thiberge, Sabine %A Ménard, Robert %A Mécheri, Salaheddine %Z This work was funded by an Institut Pasteur grant to SM. C.D.G. is supported by a post-doctoral fellowship from the Helmut Horten Foundation, Agno, Switzerland. %< avec comité de lecture %@ 2045-2322 %J Scientific Reports %I Nature Publishing Group %V 7 %N 1 %P 9129 %8 2017-08-22 %D 2017 %R 10.1038/s41598-017-09684-2 %M 28831137 %K Antimicrobial responses %K Immune evasion %Z Life Sciences [q-bio]/Immunology %Z Life Sciences [q-bio]/Human health and pathology/Infectious diseasesJournal articles %X While most subunit malaria vaccines provide only limited efficacy, pre-erythrocytic and erythrocytic genetically attenuated parasites (GAP) have been shown to confer complete sterilizing immunity. We recently generated a Plasmodium berghei (PbNK65) parasite that lacks a secreted factor, the histamine releasing factor (HRF) (PbNK65 hrfΔ), and induces in infected mice a self-resolving blood stage infection accompanied by a long lasting immunity. Here, we explore the immunological mechanisms underlying the anti-parasite protective properties of the mutant PbNK65 hrfΔ and demonstrate that in addition to an up-regulation of IL-6 production, CD4(+) but not CD8(+) T effector lymphocytes are indispensable for the clearance of malaria infection. Maintenance of T cell-associated protection is associated with the reduction in CD4(+)PD-1(+) and CD8(+)PD-1(+) T cell numbers. A higher number of central and effector memory B cells in mutant-infected mice also plays a pivotal role in protection. Importantly, we also demonstrate that prior infection with WT parasites followed by a drug cure does not prevent the induction of PbNK65 hrfΔ-induced protection, suggesting that such protection in humans may be efficient even in individuals that have been infected and who repeatedly received antimalarial drugs. %G English %Z We thank Peter Smooker and Kim Taylor (Department of Biotechnology and Environmental Biology, RMIT University, Bundoora, Australia) for providing P. berghei HRF plasmid, the CEPIA (Centre d’élevage, de production et d’infection des anopheles, Institut Pasteur, Paris) for providing Anopheles mosquitoes. We are indebted to Jacques Bellalou (Platform of the recombinant proteins, Institut Pasteur, Paris) who provided the recombinant PbHRF protein. We thank Dr. Sylvie Garcia and Malika Serra-Hassoun (Institut Pasteur, Paris) for their technical advices. We thank Pierre-Henri Commere (Imagopole, Institut Pasteur, Paris) for technical help in Facs analysis. %2 https://pasteur.hal.science/pasteur-01582002/document %2 https://pasteur.hal.science/pasteur-01582002/file/s41598-017-09684-2.pdf %L pasteur-01582002 %U https://pasteur.hal.science/pasteur-01582002 %~ INSERM %~ PASTEUR %~ CNRS %~ BIOLOGY-HOST-PARASITE-INTERACTIONS