Cell invasion by intracellular parasites – the many roads to infection

Abstract

Intracellular parasites from the genera Toxoplasma, Plasmodium, Trypanosoma, Leishmania and from the phylum Microsporidia are, respectively, the causative agents of toxoplasmosis, malaria, Chagas disease, leishmaniasis and microsporidiosis, illnesses that kill millions of people around the globe. Crossing the host cell plasma membrane (PM) is an obstacle these parasites must overcome to establish themselves intracellularly and so cause diseases. The mechanisms of cell invasion are quite diverse and include (1) formation of moving junctions that drive parasites into host cells, as for the protozoans Toxoplasma gondii and Plasmodium spp., (2) subversion of endocytic pathways used by the host cell to repair PM, as for Trypanosoma cruzi and Leishmania, (3) induction of phagocytosis as for Leishmania or (4) endocytosis of parasites induced by specialized structures, such as the polar tubes present in microsporidian species. Understanding the early steps of cell entry is essential for the development of vaccines and drugs for the prevention or treatment of these diseases, and thus enormous research efforts have been made to unveil their underlying biological mechanisms. This Review will focus on these mechanisms and the factors involved, with an emphasis on the recent insights into the cell biology of invasion by these pathogens.

Toxoplasma gondii Mechanisms of Entry Into Host Cells

“…Inside the parasite, the cytosolic domain of AMA1 binds to a parasite actin-myosin motor to allow parasite moving toward the parasitophorous vacuole in process of formation (reviewed by Horta et al, 2020). This junction allows the parasite entry and the formation of a parasitophorous vacuole that is protective to the parasite because its composition exclude proteins from the host endocytic pathways.…”

The life-cycle of Toxoplasma gondii reviewed using animations

“…They show various aspects of the structural organization of the different developmental stages of T. gondii [ 13 – 23 ]. Our analysis also considered the contributions of several other groups that have provided relevant contributions to the field [ 24 – 26 ]. All animations and images were produced using software such as 3D Max (Autodesk Inc., San Rafael, CA.…”

Caveolae as Potential Hijackable Gates in Cell Communication

“…Of note, as presented in table 1, caveolae are not exclusive entry gates for these pathogens, who "hijack" other cellular entry pathways [for an update on bacterial manipulation of clathrin see (Latomanski and Newton, 2019), for endocytotic mechanisms used by viruses, (Slonska et al, 2016)and for parasites (Horta et al, 2020)]. Furthermore, lipids enriched in caveolae could play a part in virus entry (Ewers et al, 2010)and virus replication (Favard et al, 2019), but can be found elsewhere in the plasma membrane.…”