Galectin-1-deficient mice are protected against Trypanosoma cruzi infection through altered neutrophil migration and production of reactive oxygen species and nitric oxide

Abstract

Trypanosoma cruzi is an intracellular parasite that causes Chagas disease that affects millions of people worldwide. Many cellular and molecular aspects of this neglected disease are not fully understood. Prior studies have shown that galectin-1 (Gal-1), a {beta}-galactoside-binding protein that regulates leukocyte recruitment to the inflammatory site, and promotes T. cruzi infection, but the mechanism is unclear. Here, we report that C57BL/6 mice lacking Gal-1 (Lgals1-/-) exhibited lower parasitemia and higher survival rates than their wildtype (WT) counterparts when infected with T. cruzi Y strain. Two weeks after infection, Lgals1-/- mice displayed greater neutrophil accumulation in infection site and heart tissue than WT mice. In T. cruzi-infected Lgals1-/- mice, infiltrated neutrophils produced increased levels of reactive oxygen species (ROS), while macrophages and neutrophils produced increased levels of nitric oxide (NO), which reduced replication and viability of parasites in vitro and downregulated IL-1{beta} production. Pharmacological inhibition of NADPH oxidase and NO synthase during early in vivo infection reversed the protective effect of Gal-1 deficiency in Lgals1-/- mice. Together, our findings demonstrate that lacking Gal-1 favors neutrophil migration to the infection site and increases production of ROS and NO, thereby controlling the early steps of T. cruzi infection by reducing parasitemia and prolonging survival of infected mice.