Macrophages facilitate the excystation and differentiation of Toxoplasma gondii sporozoites into tachyzoites following oocyst internalisation

Wesley P Freppel (1) , Pierre-Henri P Puech (2) , David P Ferguson (3) , Nadine P Azas (1) , Jitender P Dubey (4) , Aurélien Dumètre (1)

1 IP-TPT - Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques
2 LAI - Adhésion et Inflammation
3 University of Oxford
4 Animal Parasitic Diseases Laboratory [Beltsville, USA]

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.

Domaines: Parasitologie; Immunité innée

Wesley P Freppel, Pierre-Henri P Puech, David P Ferguson, Nadine P Azas, Jitender P Dubey, et al.. Macrophages facilitate the excystation and differentiation of Toxoplasma gondii sporozoites into tachyzoites following oocyst internalisation. Scientific Reports, 2016, 6, pp.33654. ⟨10.1038/srep33654⟩. ⟨hal-01474672⟩