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-inflammatory and immunoregulatory effects. However, its expression and function have not been assessed in the context of an infectious disease. The present study documents, for the first time, the regulated expression of galectin-1 in 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 isolated from Trypanosoma cruzi-infected mice were exposed to increasing concentrations of galectin-1. While low concentrations of this protein increased parasite replication and did not affect macrophage survival, higher inflammatory doses of galectin-1 were able to commit cells to apoptosis and inhibited parasite replication. Furthermore, galectin-1 at its lowest concentration was able to down-regulate critical mediators for parasite killing, such as interleukin 12 (IL-12) and nitric oxide, while it did not affect IL-10 secretion. Finally, endogenous galectin-1 was found to be up-regulated and secreted by the J774 macrophage cell line cultured in the presence of trypomastigotes. This result was extended in vivo by Western blot analysis, flow cytometry, and reverse transcription-PCR using macrophages isolated from T. cruzi-infected mice. This study documents the first association between galectin-1's immunoregulatory properties and its role in infection and provides new clues to the understanding of the mechanisms implicated in host-parasite interactions during Chagas' disease and other parasite infections.
Zúñiga
E
E
Departmento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Gruppi
A
A
Hirabayashi
J
J
Kasai
K I
KI
Rabinovich
G A
GA
D000276:Adjuvants, Immunologic; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D037483:Galectin 1; D006388:Hemagglutinins / Q000235:genetics* / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D011817:Rabbits; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000502:physiology*; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D037483:Galectin 1; D006388:Hemagglutinins; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide