Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics

Abstract

Neglected tropical diseases (NTDs) constitute a group of diseases that generally develop in tropical or subtropical climatic conditions and are related to poverty. Within the spectrum of NTDs, diseases caused by protozoa such as malaria, Chagas disease, and leishmaniasis exhibit elevated mortality rates, thereby constituting a substantial public health concern. Beyond their protozoan etiology, these NTDs share other similarities, such as the challenge of control and the lack of affordable, safe, and effective drugs. In view of the above, the need to explore novel diagnostic predictors and therapeutic targets for the treatment of these parasitic diseases is evident. In this context, galectins are attractive because they are a set of lectins bound to β-galactosides that play key roles in a variety of cellular processes, including host-parasite interaction such as adhesion and entry of parasites into the host cells, and participate in antiparasitic immunity in either a stimulatory or inhibitory manner, especially the galectins-1, -2, -3, and -9. These functions bestow upon galectins significant therapeutic prospects in the context of managing and diagnosing NTDs. Thus, the present review aims to elucidate the potential role of galectins in the diagnosis and treatment of malaria, leishmaniasis, and Chagas disease.

Keywords: Chagas disease; galectins; leishmaniasis; malaria.

Figure 1

Structure of galectins. Mammalian galectins are classified into three subclasses based on their structure: single CRD, two CRDs in tandem, and chimeric type. They form dynamic lattice structures by interacting with cell-surface glycoprotein receptors, influencing diverse biological processes such as adhesion, migration, invasion, nutrient transport, and cell cycle regulation.

Figure 2

Galectins-2, -3, and -9 play crucial roles in Plasmodium infection, contributing to the development of severe malaria in aging populations, the exacerbation of cerebral malaria, and acute lung injury. Additionally, it is a protective molecule that regulates parasite load in P. yoelii infections.

Figure 3

Main findings regarding the roles of Galectins during experimental models of Leishmaniasis. Gal-galectin; DAMP, damage-associated molecular pattern; PAMP, pathogen-associated molecular pattern; TReg, regulatory T-cell; KO, knockout; IL, interleukin; Th, helper T-cell.

Figure 4

Different functions of galectins in Chagas disease. Different galectins are present in the heart, acting in the expansion of T-cells and activation of apoptosis by T lymphocytes (Gal-1), as well as in increasing fibrosis, inflammation, and prevention of T. cruzi infection (Gal-1 and Gal-3); in the gastrointestinal tract, we have the presence of Gal-1, Gal-3, and Gal-9, which act in the regeneration of ganglion cells; Gal-7 and Gal-8 assist in parasitic invasion into host cells, as well as in the regulation of cellular and anti-inflammatory functions, respectively, in T. cruzi epimastigotes.