Galectins in Chagas Disease: A Missing Link Between Trypanosoma cruzi Infection, Inflammation, and Tissue Damage

Abstract

Trypanosoma cruzi, the protozoan parasite causative agent of Chagas disease, affects about seven million people worldwide, representing a major global public health concern with relevant socioeconomic consequences, particularly in developing countries. In this review, we discuss the multiple roles of galectins, a family of β-galactoside-binding proteins, in modulating both T. cruzi infection and immunoregulation. Specifically, we focus on galectin-driven circuits that link parasite invasion and inflammation and reprogram innate and adaptive immune responses. Understanding the dynamics of galectins and their β-galactoside-specific ligands during the pathogenesis of T. cruzi infection and elucidating their roles in immunoregulation, inflammation, and tissue damage offer new rational opportunities for treating this devastating neglected disease.

Keywords: Chagas disease; Trypanosoma cruzi; galectin; galectin-1; galectin-3.

FIGURE 1

(A) Structural classification of galectins. Some members of the prototype (galectin-1 and -7), chimera-type (galectin-3), and tandem-repeat type (galectins-8 and -9) galectins have been associated with T. cruzi recognition. (B) Galectins preferentially recognize parasite stages found in the mammalian host (amastigotes and trypomastigotes). Only galectin-7 recognizes epimastigotes (not shown). Potential receptors that bind human galectins (upper panel) and the intensity of some of these interactions reported by Pineda et al. (2015a) and others are summarized here (lower panel). Target cells, cellular localization, and/or properties of endogenous galectins during T. cruzi infection are enumerated in the lower panel. Ssp-4, stage-specific protein 4; AgC10, surface mucin AgC10; GP63, surface protease 63; GP82-90, surface glycoprotein (82–90); TcMUCII, T. cruzi mucin II; TS, trans-sialidase; Sp-1, surface protein 1.