title: Endothelial transmigration by Trypanosoma cruzi.
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.
authors: Departments of Pediatrics and Pathology, Northwestern University, Chicago, Illinois, United States of America.
authors: Bria M
authors: BM
authors: Coates
authors: David P
authors: DP
authors: Sullivan
authors: Ming Y
authors: MY
authors: Makanji
authors: Nga Y
authors: NY
authors: Du
authors: Cheryl L
authors: CL
authors: Olson
authors: William A
authors: WA
authors: Muller
authors: David M
authors: DM
authors: Engman
authors: Conrad L
authors: CL
authors: Epting
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002199:Capillary Permeability; D002598:Chagas Cardiomyopathy / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000469:parasitology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D008297:Male; D051379:Mice; D014349:Trypanosoma cruzi / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D001920:Bradykinin