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Trypanosoma cruzi recognition by macrophages and muscle cells: perspectives after a 15-year study
T C De Araujo-Jorge1, H S Barbosa, M N Meirelles
1Departamento de Ultraestrutura e Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brasil.
Abstract:
Macrophages and muscle cells are the main targets for invasion of Trypanosoma cruzi. Ultrastructural studies of this phenomenon in vitro showed that invasion occurs by endocytosis, with attachment and internalization being mediated by different components capable of recognizing epi- or trypomastigotes (TRY). A parasitophorus vacuole was formed in both cell types, thereafter fusing with lysosomes. Then, the mechanism of T. cruzi invasion of host cells (HC) is essentially similar (during a primary infection in the absence of a specific immune response), regardless of whether the target cell is a professional or a non-professional phagocytic cell. Using sugars, lectins, glycosidases, proteinases and proteinase inhibitors, we observed that the relative balance between exposed sialic acid and galactose/N-acetyl galactosamine (GAL) residues on the TRY surface, determines the parasite's capacity to invade HC, and that lectin-mediated phagocytosis with GAL specificity is important for internalization of T. cruzi into macrophages. On the other hand, GAL on the surface of heart muscle cells participate on TRY adhesion. TRY need to process proteolytically both the HC and their own surface, to expose the necessary ligands and receptors that allow binding to, and internalization in the host cell. The diverse range of molecular mechanisms which the parasite could use to invade the host cell may correspond to differences in the available "receptors" on the surface of each specific cell type. Acute phase components, with lectin or proteinase inhibitory activities (alpha-macroglobulins), may also be involved in T. cruzi-host cell interaction.
Insights
Trypanosoma cruzi invades host cells like macrophages and muscle cells via endocytosis. Surface sugars, specifically sialic acid and galactose/N-acetyl galactosamine, are crucial for this invasion process.
Area of Science:
- Cell Biology
- Parasitology
- Molecular Biology
Background:
- Macrophages and muscle cells are primary targets for Trypanosoma cruzi invasion.
- Parasite entry into host cells occurs through endocytosis.
Purpose of the Study:
- To elucidate the molecular mechanisms of Trypanosoma cruzi invasion into host cells.
- To investigate the role of surface molecules in parasite-host cell interactions.
Main Methods:
- In vitro ultrastructural studies.
- Use of sugars, lectins, glycosidases, proteinases, and proteinase inhibitors.
- Analysis of surface molecule interactions.
Main Results:
- Parasite invasion involves endocytosis, forming a parasitophorus vacuole that fuses with lysosomes.
- The balance of sialic acid and galactose/N-acetyl galactosamine on the parasite surface dictates invasion efficiency.
- Lectin-mediated phagocytosis with galactose specificity is key for macrophage invasion, while galactose aids adhesion to heart muscle cells.
- Proteolytic processing of both parasite and host cell surfaces is necessary for binding and internalization.
Conclusions:
- Trypanosoma cruzi invasion mechanisms are similar across different host cell types.
- Surface carbohydrate and protein interactions are critical for parasite entry.
- Host cell receptors and parasite ligands play specific roles in mediating invasion.