Endothelial transmigration by trypanosoma cruzi

Bria M. Coates, David P. Sullivan, Ming Y. Makanji, Nga Y. Du, Cheryl L. Olson, William A. Muller, David M. Engman, Conrad L. Epting

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Article numbere81187
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 2 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint

Dive into the research topics of 'Endothelial transmigration by trypanosoma cruzi'. Together they form a unique fingerprint.

Cite this