Regulated expression and effect of galectin-1 on Trypanosoma cruzi-infected macrophages: Modulation of microbicidal activity and survival

Galectin-1 is a beta -galactoside-binding protein with potent anti-inflamma tory and immunoregulatory effects. However, its expression and function hav e not been assessed in the context of an infectious disease. The present st udy documents, for the first time, the regulated expression of galectin-1 i n the context of an infectious process and its influence in the modulation of macrophage microbicidal activity and survival. A biphasic modulation in parasite replication and cell viability was observed when macrophages isola ted from Trypanosoma cruzi-infected mice were exposed to increasing concent rations of galectin-1. While low concentrations of this protein increased p arasite replication and did not affect macrophage survival, higher inflamma tory doses of galectin-1 were able to commit cells to apoptosis and inhibit ed parasite replication. Furthermore, galectin-1 at its lowest concentratio n was able to down-regulate critical mediators for parasite killing, such a s interleukin 12 (IL-12) and nitric oxide, while it did not affect IL-10 se cretion. Finally, endogenous galectin-1 was found to be up-regulated and se creted by the J774 macrophage cell line cultured in the presence of trypoma stigotes. This result was extended in vivo by Western blot analysis, flow c ytometry, and reverse transcription-PCR using macrophages isolated from T. cruzi-infected mice. This study documents the first association between gal ectin-1's immunoregulatory properties and its role in infection and provide s new clues to the understanding of the mechanisms implicated in host-paras ite interactions during Chagas' disease and other parasite infections.