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...

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Autores principales:	Claudia Demarta-Gatsi, Roger Peronet, Leanna Smith, Sabine Thiberge, Robert Ménard, Salaheddine Mécheri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95149685224d4ca18f02fb78631c3175
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spelling	oai:doaj.org-article:95149685224d4ca18f02fb78631c31752021-12-02T12:32:04ZImmunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite10.1038/s41598-017-09684-22045-2322https://doaj.org/article/95149685224d4ca18f02fb78631c31752017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09684-2https://doaj.org/toc/2045-2322Abstract 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.Claudia Demarta-GatsiRoger PeronetLeanna SmithSabine ThibergeRobert MénardSalaheddine MécheriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Demarta-Gatsi Roger Peronet Leanna Smith Sabine Thiberge Robert Ménard Salaheddine Mécheri Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite
description	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.
format	article
author	Claudia Demarta-Gatsi Roger Peronet Leanna Smith Sabine Thiberge Robert Ménard Salaheddine Mécheri
author_facet	Claudia Demarta-Gatsi Roger Peronet Leanna Smith Sabine Thiberge Robert Ménard Salaheddine Mécheri
author_sort	Claudia Demarta-Gatsi
title	Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite
title_short	Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite
title_full	Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite
title_fullStr	Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite
title_full_unstemmed	Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite
title_sort	immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (hrf) of the parasite
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/95149685224d4ca18f02fb78631c3175
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Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite

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