Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite.

Abstract : 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.
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Claudia Demarta-Gatsi, Roger Peronet, Leanna Smith, Sabine Thiberge, Robert Ménard, et al.. Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite.. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.9129. ⟨https://www.nature.com/articles/s41598-017-09684-2⟩. ⟨10.1038/s41598-017-09684-2⟩. ⟨pasteur-01582002⟩

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