Protection against malaria in mice is induced by blood stage-arresting histamine-releasing factor (HRF)-deficient parasites.

Autor:	Demarta-Gatsi C; Unité de Biologie des Interactions Hôte Parasites, Centre National de la Recherche Scientifique ERL9195, Institut National de la Santé et de la Recherche Médicale U1201, Institut Pasteur, F-75015 Paris, France., Smith L; Unité de Biologie des Interactions Hôte Parasites, Centre National de la Recherche Scientifique ERL9195, Institut National de la Santé et de la Recherche Médicale U1201, Institut Pasteur, F-75015 Paris, France., Thiberge S; Unité de Biologie et Génétique du Paludisme, Institut Pasteur, F-75015 Paris, France., Peronet R; Unité de Biologie des Interactions Hôte Parasites, Centre National de la Recherche Scientifique ERL9195, Institut National de la Santé et de la Recherche Médicale U1201, Institut Pasteur, F-75015 Paris, France., Commere PH; Imagopole, Institut Pasteur, F-75015 Paris, France., Matondo M; Spectrométrie de Masse Structurale et Protéomique, Institut Pasteur, F-75015 Paris, France., Apetoh L; Institut National de la Santé et de la Recherche Médicale U866, Université Bourgogne Franche-Comté et Centre Georges François Leclerc, 21000 Dijon, France., Bruhns P; Anticorps en Thérapie et Pathologie, Institut National de la Santé et de la Recherche Médicale U1222, Institut Pasteur, F-75015 Paris, France., Ménard R; Unité de Biologie et Génétique du Paludisme, Institut Pasteur, F-75015 Paris, France., Mécheri S; Unité de Biologie des Interactions Hôte Parasites, Centre National de la Recherche Scientifique ERL9195, Institut National de la Santé et de la Recherche Médicale U1201, Institut Pasteur, F-75015 Paris, France smecheri@pasteur.fr.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2016 Jul 25; Vol. 213 (8), pp. 1419-28. Date of Electronic Publication: 2016 Jul 18.
DOI:	10.1084/jem.20151976
Abstrakt:	Although most vaccines against blood stage malaria in development today use subunit preparations, live attenuated parasites confer significantly broader and more lasting protection. In recent years, Plasmodium genetically attenuated parasites (GAPs) have been generated in rodent models that cause self-resolving blood stage infections and induce strong protection. All such GAPs generated so far bear mutations in housekeeping genes important for parasite development in red blood cells. In this study, using a Plasmodium berghei model compatible with tracking anti-blood stage immune responses over time, we report a novel blood stage GAP that lacks a secreted factor related to histamine-releasing factor (HRF). Lack of HRF causes an IL-6 increase, which boosts T and B cell responses to resolve infection and leave a cross-stage, cross-species, and lasting immunity. Mutant-induced protection involves a combination of antiparasite IgG2c antibodies and FcγR(+) CD11b(+) cell phagocytes, especially neutrophils, which are sufficient to confer protection. This immune-boosting GAP highlights an important role of opsonized parasite-mediated phagocytosis, which may be central to protection induced by all self-resolving blood stage GAP infections. (© 2016 Demarta-Gatsi et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu