From lysosomes into the cytosol: the intracellular pathway of Trypanosoma cruzi

The protozoan parasite Trypanosoma cruzi invades a wide variety of vertebrate cells, by a mechanism distinct from phagocytosis. No pseudopods or other host cell surface alterations are observed during trypanosome entry, and invasion is enhanced after actin filaments are disrupted with cytochalasin D. These observations created a puzzle; what is the origin of the membrane required to form the intracellular vacuoles, if it is not originated from the host cell plasma membrane? Recent observations provided the answer: during cell invasion T. cruzi recruits host lysosomes, which gradually fuse with the plasma membrane at the site of parasite entry. The membrane of the parasitophorous vacuole is, therefore, very similar if not identical to the membrane of lysosomes. Lgps, major glycoproteins from mammalian lysosomes, are desialylated by a glycosylphosphatidylinositol (GPI)-anchored trans-sialidase present on the surface of trypomastigote forms. Lack of sialic acid on lgps facilitates membrane lysis by a parasite-secreted molecule, Tc-TOX, that has membrane pore-forming activity at acidic pH. We propose a sequential model in which these trypanosome products would promote parasite entry into host cells and their subsequent liberation into the cytosol.