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Published on: September 30, 2017
Endothelial transmigration by Trypanosoma cruzi
Bria M Coates1, David P Sullivan, Ming Y Makanji
1Departments of Pediatrics and Pathology, Northwestern University, Chicago, Illinois, United States of America.
Insights
Trypanosoma cruzi, the parasite causing Chagas heart disease, can rapidly cross the endothelial barrier without causing infection or damaging blood vessels. Bradykinin and CCL2 enhance this parasite transmigration.
Area of Science:
- Parasitology
- Cardiovascular Disease Research
- Cell Biology
Background:
- Chagas heart disease, a major cause of heart failure in Latin America, stems from Trypanosoma cruzi infection.
- The mechanism by which T. cruzi crosses the endothelial barrier to infect tissues from the bloodstream remains largely undescribed.
- Understanding T. cruzi-endothelial interactions is crucial for developing therapies against Chagas disease pathogenesis.
Purpose of the Study:
- To investigate the transmigration of T. cruzi across endothelial cells in vitro.
- To identify factors that facilitate parasite dissemination through the vascular endothelium.
- To explore novel therapeutic targets for Chagas disease.
Main Methods:
- Adapted leukocyte transmigration assays to study T. cruzi interaction with endothelial cells.
- Utilized in vitro models to observe and quantify parasite migration across endothelial monolayers.
- Investigated the role of bradykinin and the chemokine CCL2 in parasite transmigration.
Main Results:
- Provided the first evidence of rapid T. cruzi transmigration across endothelial cells.
- Demonstrated that transmigration is distinct from productive infection and does not compromise endothelial barrier integrity.
- Identified bradykinin as a facilitator and CCL2 as an enhancer of T. cruzi transmigration.
Conclusions:
- T. cruzi can efficiently cross the endothelial barrier via a non-infectious, non-disruptive mechanism.
- Bradykinin and CCL2 play significant roles in facilitating parasite dissemination.
- These findings offer new insights into Chagas disease pathogenesis and potential therapeutic strategies.
Abstract:
Chagas heart disease, the leading cause of heart failure in Latin America, results from infection with the parasite Trypanosoma cruzi. Although T. cruzi disseminates intravascularly, how the parasite contends with the endothelial barrier to escape the bloodstream and infect tissues has not been described. Understanding the interaction between T. cruzi and the vascular endothelium, likely a key step in parasite dissemination, could inform future therapies to interrupt disease pathogenesis. We adapted systems useful in the study of leukocyte transmigration to investigate both the occurrence of parasite transmigration and its determinants in vitro. Here we provide the first evidence that T. cruzi can rapidly migrate across endothelial cells by a mechanism that is distinct from productive infection and does not disrupt monolayer integrity or alter permeability. Our results show that this process is facilitated by a known modulator of cellular infection and vascular permeability, bradykinin, and can be augmented by the chemokine CCL2. These represent novel findings in our understanding of parasite dissemination, and may help identify new therapeutic strategies to limit the dissemination of the parasite.
