Anti-galectin-1 autoantibodies in humanTrypanosoma cruziinfection: differential expression of thisβ-galactoside-binding protein in cardiac Chagas' disease

Abstract

SUMMARYThe pathogenesis of Chagas' disease has been subject of active research and still remains to be ascertained. Galectin-1 (Gal-1), a member of a conserved family of animal b-galactoside-binding proteins, localized in human heart tissue, has been suggested to play key roles in immunological and inflammatory processes. In the present study we demonstrated the occurrence of anti-Gal-1 autoAb in sera from patients in the acute and chronic stages of Chagas' disease (ACD and CCD) by means of ELISA and Western blot analysis. We found a marked increase in the level and frequency of Ig E antiGal-1 antibodies in sera from patients with ACD, but a low frequency of Ig M anti-Gal-1 immunoreactivity. Moreover, Ig G immunoreactivity to this b-galactoside-binding protein was found to be correlated with the severity of cardiac damage in CCD, but was absent in nonrelated cardiomyopathies. We could not detect immunoreactivity with Trypanosoma cruzi antigens using a polyclonal antibody raised to human Gal-1 and no hemagglutinating activity could be specifically eluted from a lactosyl-agarose matrix from parasite lysates. Moreover, despite sequence homology between Gal-1 and shed acute phase antigen (SAPA) of T. cruzi, anti-Gal-1 antibodies eluted from human sera failed to cross-react with SAPA. In an attempt to explore whether Gal-1 immunoreactivity was originated from endogenous human Gal-1, we finally investigated its expression levels in cardiac tissue (the main target of Chagas' disease). This protein was found to be markedly upregulated in cardiac tissue from patients with severe CCD, compared to cardiac tissue from normal individuals.

Trypanosoma cruzi Infection Imparts a Regulatory Program in Dendritic Cells and T Cells via Galectin-1–Dependent Mechanisms

“…Previous studies demonstrated the expression of Gal-1 in T. cruzi-infected immune cells (35,36). Moreover, in human settings, this lectin has been shown to be prominently expressed in cardiac tissue from patients with severe chronic Chagas' disease (50). In this study, we demonstrate a tolerogenic role for Gal-1 during acute T. cruzi infection.…”

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

“…We have previously shown that anti-Gal-8 autoantibodies produced by SLE patients block the interaction of Gal-8 with β1 integrins involved in its apoptotic action upon activated T cells (Norambuena et al, 2009). Autoantibodies against diff erent members of the galectin family such as Gal-1, -2, -3, and -4 been detected in patients with diff erent types of autoimmune diseases and in cancer (Lutomski et al, 1997;Giordanengo et al, 2001;Jensen-Jarolim et al, 2001;Lim et al, 2002;Romero et al, 2006;Montiel et al, 2010). However, whether autoantibodies against galectins interfere with galectin function in the immune system and whether they play pathogenic roles are poorly studied.…”

Binding of Toxoplasma gondii Glycosylphosphatidylinositols to Galectin-3 Is Required for Their Recognition by Macrophages

“…Endogenous galectin-1 expression is up-regulated in vitro and in vivo by T. cruzi, and the expression of galectin-1 is up-regulated in cardiac tissue from patients with chronic Chagas disease (31). Because the adhesion of T. cruzi to heart muscle cells is mediated by protein-carbohydrate interactions, an overexpression of galectin-1 on heart tissue could facilitate parasite invasion toward this vulnerable infection site (32).…”