Date Published: October 9, 2015
Publisher: Public Library of Science
Author(s): Alejandro F. Benatar, Gabriela A. García, Jacqeline Bua, Juan P. Cerliani, Miriam Postan, Laura M. Tasso, Jorge Scaglione, Juan C. Stupirski, Marta A. Toscano, Gabriel A. Rabinovich, Karina A. Gómez, Ana Rodriguez. http://doi.org/10.1371/journal.pntd.0004148
Abstract: BackgroundChronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection.Methodology and Principal FindingsHere we investigated the contribution of galectin–1 (Gal–1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T. cruzi infection, particularly in the context of cardiac pathology. We found that exposure of HL–1 cardiac cells to Gal–1 reduced the percentage of infection by two different T. cruzi strains, Tulahuén (TcVI) and Brazil (TcI). In addition, Gal–1 prevented exposure of phosphatidylserine and early events in the apoptotic program by parasite infection on HL–1 cells. These effects were not mediated by direct interaction with the parasite surface, suggesting that Gal–1 may act through binding to host cells. Moreover, we also observed that T. cruzi infection altered the glycophenotype of cardiac cells, reducing binding of exogenous Gal–1 to the cell surface. Consistent with these data, Gal–1 deficient (Lgals1-/-) mice showed increased parasitemia, reduced signs of inflammation in heart and skeletal muscle tissues, and lower survival rates as compared to wild-type (WT) mice in response to intraperitoneal infection with T. cruzi Tulahuén strain.Conclusion/SignificanceOur results indicate that Gal–1 modulates T. cruzi infection of cardiac cells, highlighting the relevance of galectins and their ligands as regulators of host-parasite interactions.
Partial Text: Chagas disease, caused by infection with the protozoan parasite Trypanosoma cruzi, represents the main cause of infectious heart disease in Latin America. It is estimated that about 8 to 10 million people worldwide are infected with T. cruzi, mostly in Central and South America where Chagas disease is endemic [1,2]. In the last decade, an increased number of cases has been well documented in North America, Europe and Western Pacific, mostly because of the influx of immigrants from endemic countries [3–5].
The interaction between parasite and host cells is crucial for T. cruzi survival involving the recognition of a large number of ligands and/or receptors on the surface of both the parasite and the host cells [37–41]. With regards to cardiomyocytes, carbohydrate residues of membrane glycoconjugates, like galactosyl, mannosyl, and sialyl residues, together with mannose receptors not only participate in parasite entry but are also regulated by the infection itself . Intracellularly, the parasite takes control of host cells, including cardiomyocytes which respond to infection with the production of cytokines, chemokines, metalloproteinases, and glycan-binding proteins .