Up-regulation of galectin-3 and its ligands by Trypanosoma cruzi infection with modulation of adhesion and migration of murine dendritic cells

Abstract

The impact of a pathogen-induced inflammatory response on dendritic cells (DCs) and on their expression of galectin-3 (Gal-3) was studied on splenic DCs (sDCs) from Trypanosoma cruzi-infected mice. We determined the lectin expression and also presentation of ligands using the labeled galectin as probe. By reverse transcriptase polymerase chain reaction, western blot analysis, quantitative glycocytochemistry, and computer-assisted quantitative microscopy, we demonstrate that, in sDCs from infected mice, expression of Gal-3 and Gal-3-specific ligands were markedly up-regulated and adhesiveness was increased with Gal-3-coated substratum. Gal-3 expression was also enhanced in T. cruzi-infected D2SC-1 cells. To assess influence on migration, we had to work exclusively with D2SC-1 cells because sDCs rapidly lost their capacity to adhere to substratum. Migration of infected- and TCM-treated D2SC-1 cells were reduced when substratum was coated with Gal-3. Expression of Gal-3 by D2SC-1 was reduced when they were incubated with anti-Gal-3 antisense oligonucleotide without effect on cell invasion by the parasite. By using seven neoglycoconjugates, we probed the cellular capacity to specifically bind carbohydrate ligands. Similar to Gal-3, an up-regulation was noted with respect to sites specific for Man and alpha-GalNAc, respectively, revealing that infection-dependent changes are not confined to Gal-3-dependent parameters. Considered together, these data document for the first time that a parasitic infection can modulate both in vivo and in vitro the expression of Gal-3 and of ligands for this lectin in DCs with functional consequences on their capacities of adhesion and migration. These results suggest a new immunomodulatory property of T. cruzi.

Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

“…Galectins, such as galectin-1 and galectin-3, are upregulated after pathogen invasion and may serve as a regulator in innate defense during inflammation (6,8,28,47). In the present study, we show in vivo that galectin-1 was upregulated in mice after influenza virus infection, and its levels positively correlated with viral loads.…”

Galectin-9 Induces Maturation of Human Monocyte-Derived Dendritic Cells

“…Therefore, it is possible that the up-regulation of Gal-9 expression in DCs or other cells in response to such factors is responsible for the induction of DC maturation. Recently, Vray et al (45) have shown that Trypanosoma cruzi infection up-regulated the expression of Gal-3 and of its ligands in DCs with functional consequences on their capacities of adhesion and migration, indicating Gal may play important roles in modulation of DCs. Our results suggest that Gal-9 plays an important role not only in innate immunity by modulating granulocyte functions but also in acquired immunity by inducing DC maturation.…”

Transfection ofTrypanosoma cruziwith Host CD40 Ligand Results in Improved Control of Parasite Infection

“…T. cruzi trypomastigotes (Y strain) were maintained by weekly intraperitoneal inoculation into male BALB/c mice (6 to 8 weeks old; Bantin & Kingman Universal, Hull, Humberside, United Kingdom) with 100 blood form trypomastigotes in 0.2 ml of phosphate-buffered saline (PBS) on day 0. For challenge infections, the Tehuantepec strain of T. cruzi was maintained in mice like the Y strain and used as previously described (13,33,52,53,56).…”