Related Experiment Video
Updated: Jun 16, 2026
Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
Induced pluripotent stem cell-derived human macrophages as an infection model for Trypanosoma cruzi
Lore Baert1,2, Monica Cal1,2, Thierry Doll3
1Dept. Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute (Swiss TPH), Allschwil, Switzerland.
Insights
Developing a new assay using human stem cell-derived macrophages (iMACs) is crucial for finding Chagas disease drugs that ensure a complete cure, addressing limitations of current treatments.
Area of Science:
- Parasitology
- Stem Cell Biology
- Drug Discovery
Background:
- Chagas disease, caused by Trypanosoma cruzi, affects millions globally with suboptimal treatments, especially for chronic infections.
- Existing drugs like posaconazole have failed in clinical trials, highlighting the need for assays predicting sterile cure.
- Assessing recrudescence post-treatment is vital for developing effective Chagas disease therapies.
Purpose of the Study:
- To establish a human cell-based assay for screening Chagas disease therapeutics.
- To evaluate human induced pluripotent stem cell-derived macrophages (iMACs) as a host model for Trypanosoma cruzi.
- To assess the potential of iMACs for long-term studies on parasite recrudescence.
Main Methods:
- Utilized human induced pluripotent stem cell-derived macrophages (iMACs) as host cells for Trypanosoma cruzi infection.
- Employed fluorescently tagged parasites (mNeonGreen) and host cells (RFP) for live cell imaging and infection dynamics monitoring.
- Validated compound activity (benznidazole, posaconazole) against T. cruzi in iMACs, comparing results with established mouse macrophage models.
Main Results:
- Human iMACs demonstrated high susceptibility to T. cruzi infection.
- Live imaging allowed real-time monitoring of parasite-host cell dynamics.
- Compound activity in iMACs mirrored established models, validating the system for drug screening.
Conclusions:
- Human iMACs provide a robust, human-relevant model for studying Chagas disease and screening potential therapeutics.
- The iMAC model is suitable for long-term assays to evaluate parasite recrudescence and predict sterile cure.
- This platform facilitates host-pathogen interaction studies and advances Chagas disease drug discovery.
Abstract:
Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people globally. Unfortunately, the available treatment options, especially for the chronic stage of the disease, are suboptimal. Given the chronic nature of the disease and the elusive nature of the parasite, there is a high need for new and safer drugs that deliver sterile cure. Posaconazole was a promising lead in the drug discovery pipeline but ultimately failed in clinical trials due to patient relapses. This failure illustrates the need for a drug screening assay that can predict sterile cure by assessing recrudescence after treatment. Here, we used human induced pluripotent stem cell (iPSC)-derived macrophages (iMACs) as host cells for T. cruzi. The iMACs were highly susceptible to infection by the parasites. By combining red fluorescent protein (RFP)-expressing iMACs with mNeonGreen-expressing T. cruzi, we were able to monitor the dynamics of the infection through live cell imaging. The activity of the compounds benznidazole and posaconazole was consistent with the results of an established infection system using mouse primary macrophages. The post-mitotic nature of iMACs makes them suitable host cells for long-term assays needed to assess recrudescence of parasites. Moreover, their human origin, stable genetic background, and capacity for genetic modification make the iMACs excellent host cells for studying host-pathogen interaction.
