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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 hrf?), 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 hrf? 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 hrf?-induced protection, suggesting that such protection in humans may be efficient even in individuals that have been infected and who repeatedly received antimalarial drugs.

SUBMITTER: Demarta-Gatsi C 

PROVIDER: S-EPMC5567273 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Demarta-Gatsi Claudia C   Peronet Roger R   Smith Leanna L   Thiberge Sabine S   Ménard Robert R   Mécheri Salaheddine S  

Scientific reports 20170822 1


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 underl  ...[more]

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