| Autor: |
Demarta-Gatsi C; Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, Paris, F-75015, France.; CNRS ERL9195, Paris, F-75015, France.; INSERM U1201, Paris, F-75015, France., Peronet R; Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, Paris, F-75015, France.; CNRS ERL9195, Paris, F-75015, France.; INSERM U1201, Paris, F-75015, France., Smith L; Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, Paris, F-75015, France.; CNRS ERL9195, Paris, F-75015, France.; INSERM U1201, Paris, F-75015, France., Thiberge S; Institut Pasteur, Unité de Biologie et Génétique du Paludisme, F-75015, Paris, France., Ménard R; Institut Pasteur, Unité de Biologie et Génétique du Paludisme, F-75015, Paris, France., Mécheri S; Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, Paris, F-75015, France. smecheri@pasteur.fr.; CNRS ERL9195, Paris, F-75015, France. smecheri@pasteur.fr.; INSERM U1201, Paris, F-75015, France. smecheri@pasteur.fr. |
| Abstrakt: |
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. |
