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.
Liste complète des métadonnées

Littérature citée [64 références]  Voir  Masquer  Télécharger

https://hal-pasteur.archives-ouvertes.fr/pasteur-01582002
Contributeur : Floran Bidault <>
Soumis le : mardi 5 septembre 2017 - 14:57:15
Dernière modification le : jeudi 11 janvier 2018 - 06:28:08

Fichier

s41598-017-09684-2.pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

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〉

Partager

Métriques

Consultations de la notice

122

Téléchargements de fichiers

80