Intracellular trafficking and the parasitophorous vacuole of Leishmania mexicana-infected macrophages

Abstract

The continued success of Leishmania as an intramacrophage parasite is dependent on its ability to survive within an acidic intracellular compartment, resist degradation by lysosomal hydrolases, exploit the host cell as a source of nutrients, and avoid the macrophage's antigen-presenting capabilities. All these requirements are dependent on the properties of the parasitophorous vacuole in which Leishmania resides. This study shows that the vacuole possesses membrane proteins characteristic of a lysosome, and has MHC class II molecules. The trafficking of a variety of endocytic markers supports this finding. However, a temporal study up to 14 days post-infection indicates that, as it matures, the vacuole gains mannose 6-phosphate receptor, and becomes more accessible to endocytosed ligand, suggesting that the vacuole has functionally translocated from a lysosomal to late endosomal compartment. Endocytosed material was detected in the flagellar pocket and inside the amastigote, demonstrating parasite uptake of intra-vacuolar material. Careful analysis of amastigotes suggests that they avoid antigen presentation by their host cell by limiting the release of potential antigens. These findings significantly extend our understanding of the mechanisms employed by Leishmania to ensure its survival in the macrophage.