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.

Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023

“…Revisão recente sobre família de proteínas humanas ligantes de galactosídeos, denominadas galectinas, advoga por sua atuação significante na imunomodulação inata e adaptativa à infecção pelo T. cruzi, com potenciais implicações fisiopatológicas e terapêuticas. 263 …”

“…Recent review about the family of human galactoside-binding proteins, called galectins, has reported on their significant participation in the innate and adaptive immunomodulation to T. cruzi infection, with potential pathophysiological and therapeutical implications. 263 …”

“…Revisão recente sobre família de proteínas humanas ligantes de galactosídeos, denominadas galectinas, advoga por sua atuação significante na imunomodulação inata e adaptativa à infecção pelo T. cruzi, com potenciais implicações fisiopatológicas e terapêuticas. 263 Formas tripomastigotas transformam-se no interior das células do hospedeiro em formas amastigotas, mas, enquanto as células parasitadas se mantêm íntegras, não se observa reação inflamatória local. Quando a célula parasitada se rompe, há liberação das formas epi, tripo e amastigotas do parasito, íntegras ou degeneradas, bem como de componentes celulares que atuam como imunógenos (por exemplo mitocôndrias, restos de miofibrilas) no meio extracelular, estimulando a presença de mediadores inflamatórios, que causam vasodilatação e aumento da permeabilidade vascular, fatores tipicamente implicados na exacerbação do processo inflamatório.…”

Unraveling the role of galectin-3 in cardiac pathology and physiology

“…Gal-3 is expressed in areas of inflammation of hearts from patients with terminal Chagas’ disease ( Souza et al, 2017a ). Moreover, Gal-3 promotes T. Cruzi infection ( Poncini et al, 2021 ). Pharmacologic Gal-3 inhibition with N-acetyl-b-Lactosamine was associated with reduced oxidative stress and fibrosis in chronic infection, although no improvements were observed in physical capacity and arrhythmias ( Souza et al, 2017a ).…”

The universe of galectin-binding partners and their functions in health and disease

“…Galectins are critical regulators of a broad range of physiological processes, such as acute and chronic inflammation ( 21 , 22 ), pathogen recognition ( 23 , 24 ) and pregnancy ( 25 ), among others. Mounting evidence indicates that these proteins also play fundamental roles in cancer biology including tumor cell proliferation, angiogenesis, migration, metastasis and immune escape.…”