Lack of galectin-3 prevents cardiac fibrosis and effective immune responses in a murine model of Trypanosoma cruzi infection

Pineda, M. A. , Cuervo, H., Fresno, M., Soto, M. and Bonay, P. (2015) Lack of galectin-3 prevents cardiac fibrosis and effective immune responses in a murine model of Trypanosoma cruzi infection. Journal of Infectious Diseases, 212(7), pp. 1160-1171. (doi:10.1093/infdis/jiv185) (PMID:25805753)

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Abstract

Background. Chagas disease is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. One of the major causes of mortality in the disease is the cardiomyopathy observed in chronic patients, despite the low number of parasites detected in cardiac tissue. Galectin-3, a carbohydrate-binding protein with affinity for β-galactoside–containing glycoconjugates, is upregulated upon infection, and it has been recently involved in the pathophysiology of heart failure. Methods. We investigated the role of galectin-3 in systemic and local responses in a murine model of T. cruzi infection, using knockout animals. Molecular mechanisms underlying galectin-3–dependent inflammatory responses were further assessed in cultured dendritic cells in vitro. Results. Mice deficient for galectin-3 have elevated blood parasitemia levels and impaired cytokine production during infection. Remarkably, galectin-3 promotes cellular infiltration in the heart of infected mice and subsequent collagen deposition and cardiac fibrosis. Furthermore, we show that an unbalanced Toll-like receptor expression on antigen-presenting cells may be the cause of the impaired immune response observed in galectin-3–deficient mice in vivo. Conclusions. These results suggest that galectin-3 is strongly involved in Chagas disease, not only in the immune response against T. cruzi, but also in mediating cardiac tissue damage.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Pineda, Dr Miguel
Authors: Pineda, M. A., Cuervo, H., Fresno, M., Soto, M., and Bonay, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Infectious Diseases
Publisher:Oxford University Press
ISSN:0022-1899
ISSN (Online):1537-6613
Published Online:24 March 2015

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