Location: Animal Parasitic Diseases LaboratoryTitle: During host cell traversal and cell-to-cell passage Toxoplasma gondii sporozoites inhabit the parasotophorous vacuole and posteriorly release dense granule proteins-associated membranous trails
|TARTARELLI, IRENE - Istituto Superiore Di Sanità|
|TINARI, ANTONELLA - Istituto Superiore Di Sanità|
|POSSENTI, ALESSIA - Istituto Superiore Di Sanità|
|CHERCHI, SIMONA - Istituto Superiore Di Sanità|
|FALCHI, MARIO - Istituto Superiore Di Sanità|
|SPANO, FURIO - Istituto Superiore Di Sanità|
Submitted to: International Journal for Parasitology
Publication Type: Book / Chapter
Publication Acceptance Date: 6/23/2020
Publication Date: 11/1/2020
Citation: Tartarelli, I., Tinari, A., Possenti, A., Cherchi, S., Falchi, M., Dubey, J.P., Spano, F. 2020. During host cell traversal and cell-to-cell passage Toxoplasma gondii sporozoites inhabit the parasotophorous vacuole and posteriorly release dense granule proteins-associated membranous trails. International Journal for Parasitology. 50(13):1099-1115. https://doi.org/10.1016/j.ijpara.2020.06.012.
Interpretive Summary: Coccidia are intracellular single celled parasites infecting livestock and humans. Hosts become infected by ingesting an environmentally resistant stage (oocyst) excreted in feces of infected animals or humans. Oocysts are not infective when excreted in feces and it takes 1 day or more to become infectious (sporulated oocyst). A sporulated oocyst contains sporozoites enclosed in sporocysts. After ingestion, the parasite excyst in small intestine and sporozoites invade epithelial cells and some are carried to distant sites within hours of infection. How the parasite travels and enters host cells is not fully understood. Here, the authors found novel structures that are attached to Toxoplasma gondii sporozoites during invasion. These results will be of interest to biologists, and parasitologists.
Technical Abstract: Toxoplasma gondii has a worldwide distribution and infects virtually all warm-blooded animals, including humans. The ingestion of the environmentally resistant oocyst stage excreted only in the feces of cats is central to the transmission of this apicomplexan parasite. There is vast literature on the host and T. gondii tachyzoite (proliferative stage of the parasite) but little is known of the host-parasite interaction and conversion of the free-living stage (sporozoite inside the oocyst) to the parasitic stage. Here, we present events that follow invasion of host cells with T. gondii sporozoites by using immunofluorescence (IF) and transmission electron microscopy (TEM). Several human type cell cultures were infected with T. gondii sporozoites of the two genotypes (Type II, ME49 and Type III, VEG) most prevalent worldwide. For the first time, using anti-RON4 antibodies, the moving junction was visualized in sporozoites during the invasion process and shortly after its completion. Surprisingly, IF and TEM evaluation revealed that intracellular sporozoites release at their posterior end long membranous tails, herein named sporozoite-specific trails (SST). Differential permeabilization and IF experiments showed that the SSTs are associated with several dense granule proteins (GRAs) and that their membranous component is of parasite origin. Furthermore, TEM observations demonstrated that SST-associated sporozoites are delimited by a typical parasitophorous vacuole, which is retained during parasite exit from the host cell and during cell-to-cell passage. Our data strongly suggest that host cell traversal by T. gondii sporozoites relies on a novel force-producing mechanism, based on the massive extrusion at the parasite posterior pole of GRAs-associated membranous material derived from the same pool of membranes forming the intravacuolar network.