title: Macrophages facilitate the excystation and differentiation of Toxoplasma gondii sporozoites into tachyzoites following oocyst internalisation.
abstract: Toxoplasma gondii is a common parasite of humans and animals, which is transmitted via oocysts in cat faeces or tissue cysts in contaminated meat. The robust oocyst and sporocyst walls protect the infective sporozoites from deleterious external attacks including disinfectants. Upon oocyst acquisition, these walls lose their integrity to let the sporozoites excyst and invade host cells following a process that remains poorly understood. Given the resistance of the oocyst wall to digestive enzymes and the ability of oocysts to cause parenteral infections, the present study investigated the possible contribution of macrophages in supporting sporozoite excystation following oocyst internalisation. By using single cell micromanipulations, real-time and time-point imaging techniques, we demonstrated that RAW macrophages could interact rapidly with oocysts and engulfed them by remodelling of their actin cytoskeleton. Internalised oocysts were associated to macrophage acidic compartments and showed evidences of wall disruption. Sporozoites were observed in macrophages containing oocyst remnants or in new macrophages, giving rise to dividing tachyzoites. All together, these results highlight an unexpected role of phagocytic cells in processing T. gondii oocysts, in line with non-classical routes of infection, and open new perspectives to identify chemical factors that lead to oocyst wall disruption under physiological conditions.
authors.affiliation: Aix Marseille Université, IP-TPT UMR MD 3, Marseille, F-13385, France.
authors.forename: Wesley
authors.initials: W
authors.lastname: Freppel
authors.affiliation: Aix Marseille Université, LAI UM 61, Marseille, F-13288, France.|nserm, UMR_S 1067, Marseille, F-13288, France.|CNRS, UMR 7333, Marseille, F-13288, France.
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Puech
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom.
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.affiliation: Aix Marseille Université, IP-TPT UMR MD 3, Marseille, F-13385, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural research Center, Animal Parasitic Diseases Laboratory, Building 1001, Beltsville, MD 20705-2350, USA.
authors.forename: Jitender P
authors.initials: JP
authors.lastname: Dubey
authors.affiliation: Aix Marseille Université, IP-TPT UMR MD 3, Marseille, F-13385, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dumètre
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000378:metabolism; D008264:Macrophages / Q000469:parasitology* / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D033661:Oocysts / Q000378:metabolism* / Q000648:ultrastructure; D010587:Phagocytosis; D034101:Sporozoites / Q000502:physiology* / Q000648:ultrastructure; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000469:parasitology / Q000635:transmission
chemical_list: D000199:Actins