Host cell traversal by Toxoplasma gondii sporozoites: evidence of an unprecedented force-producing mechanism

Toxoplasma gondii systemic dissemination to the tissues of intermediate hosts (IHs) is key to parasite transmission to cat and other felids through predation. The spreading of infection is operated by the tachyzoites, whose journey to all IHs" tissues initiates from the vascularized lamina propria underlying the intestinal epithelium. To establish themselves in this strategic anatomical niche, tachyzoites rely on the capability of T. gondii transmission stages, sporozoites and bradyzoites, to exit the invaded enterocytes and reach the lamina propria, where their differentiation into fast replicating tachyzoites takes place. Sporozoites and bradyzoites migrate from the cytoplasm of IH"s enterocytes to the lamina propria as soon as 2 h post-feeding of mice with T. gondii oocysts or tissue cysts, as originally shown by transmission electron microscopy (TEM) studies [1,2]. Using an in vitro model of fibroblast infection, we showed by immunofluorescence (IF) that after host cell (HC) invasion by a moving junction-dependent mechanism, T. gondii sporozoites posteriorly release long membranous tails, named sporozoite-specific trails (SSTs), that define the trajectories followed by sporozoites during HC traversal [3]. SST production was also demostrated in the closely related coccidian Hammondia heydorni. The SSTs contain several dense granule proteins generally localized to the parasitophorous vacuole (PV) lumen (GRA1), the intravacuolar network (IVN; GRA2, GRA4, GRA6) or the PV membrane (GRA5, GRA7). Surprisingly, TEM studies demonstrated that SST-associated sporozoites reside in the PV and that this structure is retained during parasite exit from the HC and cell-to-cell passage. To investigate the role of IVN in SST formation, we generated T. gondii sporozoites lacking GRA2, which plays a central role in membrane tubulation and IVN establishment [4]. TEM and IF analysis showed that GRA2 depletion not only altered the IVN ultrastructure but also the release pattern of SSTs" constituents. Collectively, our data suggest that HC traversal by T. gondii sporozoites exploits a novel force-producing mechanism, based on the massive extrusion at the posterior pole of intravacuolar parasites of GRA-associated membranous material derived from the same pool of membranes and nanotubules that constitute the IVN.

[1] Dubey et al. 1997. PMID: 9379292.

[2] Dubey JP et al. 1997. PMID: 9435131.

[3] Tartarelli et al. 2020. PMID: 32882286.

[4] Mercier et al. 2002. PMID: 12134078.