Impact of galectin-1 on the evolution of acute experimental Trypanosoma cruzi infection / Avaliação da participação da galectina-1 na evolução da infecção experimental aguda por Trypanosoma cruzi

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Galectin-1 (Gal-1) is a -galactoside-binding protein and participates in several biological processes, including modulation of immune response. In the literature, there are several reports about the potential therapeutic use of Gal-1 for autoimmune diseases, inflammatory, degenerative and infectious diseases. However, there are few reports on the involvement of Gal-1 in disease caused by Trypanosoma cruzi. Thus, this work was conducted to study the participation of endogenous and exogenous Gal-1 in acute experimental infection by T. cruzi. Recombinant Gal-1, galectin-1-deficient mice (KO - Gal-1-/-) or wild type (WT - Gal-1+/+) mice and macrophages from these animals were used to perform the in vivo and in vitro assays. The animals were infected with trypomastigotes of T. cruzi (strain Y), intraperitoneally. The biological parameters analyzed were parasitemia and survival; histopathology of heart tissue, measurement of nitric oxide by Griess reaction; leukocyte immunophenotyping by flow cytometry; cytokine detection by ELISA and the release rate of parasites in cultured macrophages. Infected-Gal-1-/- mice or infected-Gal-1+/+ mice treated with Gal-1 showed the lowest levels of parasitemia. Interestingly, all infected-KO mice survived after the infection, whereas the infected-WT mice showed a drastic reduction in survival. The absence of endogenous Gal-1 or the exogenous Gal-1 treatment promoted a drastic reduction on inflammatory cells infiltrate in the cardiac muscle of infected mice. The sera of infected-WT mice treated with Gal-1, but not untreated animals, showed high levels of IFN-. Additionally, sera from infected-KO mice showed lower levels of different cytokines (TNF-, IFN-, IL-4, IL-10 and IL-12) compared with serum samples from infected-WT animals. The number of spleen cells (T, B cells, macrophages, NK and NKT) were generally higher in WT mice than in KO mice after infection with T. cruzi. Interestingly, the peritoneal cavity of infected-KO mice presented an increased numbers of neutrophils and macrophages after 12h or 24h of infection, respectively. The peak of NO production induced by T. cruzi in Gal-1-/- macrophages was earlier and more intense than that obtained by Gal-1+/+ macrophage. Furthermore, Gal-1-/- macrophage released fewer parasites in vitro in comparison to Gal-1+/+ macrophages. Taken together, these results suggest that the absence of endogenous Gal-1 or treatment with exogenous Gal-1 promoted immunological profiles (innate and adaptative responses) that cooperate to the resolution of acute experimental infection by T. cruzi

ASSUNTO(S)

trypanosoma cruzi immunoregulation galectin-1 galectina-1 trypanosoma cruzi lectin lectina infecção imunorregulação. infection

ACESSO AO ARTIGO

Documentos Relacionados